Advertisement

ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI184172

Antithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis

Thomas Mandel Clausen,1 Ryan J. Weiss,1 Jacob R. Tremblay,2 Benjamin P. Kellman,3 Joanna Coker,4 Leo A. Dworkin,5 Jessica P. Rodriguez,1 Ivy M. Chang,1 Timothy Chen,1 Vikram Padala,1 Richard Karlsson,6 Hyemin Song,2 Kristina L. Peck,2 Satoshi Ogawa,2 Daniel R. Sandoval,1 Hiren J. Joshi,6 Gaowei Wang,7 L. Paige Ferguson,8 Nikita Bhalerao,9 Allison Moores,10 Tannishtha Reya,8 Maike Sander,7 Thomas C. Caffrey,11 Jean L. Grem,12 Alexandra Aicher,13 Christopher Heeschen,14 Dzung Le,15 Nathan E. Lewis,5 Michael A. Hollingsworth,11 Paul M. Grandgenett,11 Susan L. Bellis,16 Rebecca L. Miller,6 Mark M. Fuster,17 David W. Dawson,18 Dannielle D. Engle,2 and Jeffrey D. Esko1

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Clausen, T. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Weiss, R. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Tremblay, J. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Kellman, B. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Coker, J. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Dworkin, L. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Rodriguez, J. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Chang, I. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Chen, T. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Padala, V. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Karlsson, R. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Song, H. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Peck, K. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Ogawa, S. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Sandoval, D. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Joshi, H. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Wang, G. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Ferguson, L. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Bhalerao, N. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Moores, A. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Reya, T. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Sander, M. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Caffrey, T. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Grem, J. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Aicher, A. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Heeschen, C. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Le, D. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Lewis, N. in: PubMed | Google Scholar |

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Hollingsworth, M. in: PubMed | Google Scholar |

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Grandgenett, P. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Bellis, S. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Miller, R. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Fuster, M. in: PubMed | Google Scholar

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Dawson, D. in: PubMed | Google Scholar |

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Engle, D. in: PubMed | Google Scholar |

1Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America

2Salk Institute for Biological Studies, La Jolla, United States of America

3Ragon Institute of MGH, MIT, and Harvard, Cambridge, United States of America

4Biomedical Sciences Graduate Program, UCSD, La Jolla, United States of America

5Departments of Pediatrics and Bioengineering, UCSD, La Jolla, United States of America

6Copenhagen Center for Glycomics, Department of Cellular and Molecular Medi, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

7Department of Pediatrics, Pediatric Diabetes Research Center, Sanford Consortium for Regenerative Medicine, UCSD, La Jolla, United States of America

8Department of Pharmacology and Medicine, UCSD, La Jolla, United States of America

9Division of Hematology-Oncology, University of Massachusetts Medical School, Worchester, United States of America

10Bishops School, La Jolla, United States of America

11Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America

12Department of Internal Medicine, University of Nebraska Medical Center, Omaha, United States of America

13Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

14Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, Candiolo, Italy

15Department of Pathology, UCSD, La Jolla, United States of America

16Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States of America

17VA San Diego Healthcare System, La Jolla, United States of America

18Department of Pathology and Laboratory Medicine and Jonsson Comprehensive C, David Geffen School of Medicine at UCLA, Los Angeles, United States of America

Find articles by Esko, J. in: PubMed | Google Scholar

Published September 16, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI184172.
Copyright © 2025, Clausen et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 16, 2025 - Version history
View PDF
Abstract

3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid. Here we show that HSAT is ubiquitously expressed in the basement membranes of epithelial cells in multiple tissues. In the pancreas, HSAT is expressed by healthy ductal cells and its expression is increased in premalignant pancreatic intraepithelial neoplasia lesions (PanINs), but not in pancreatic ductal adenocarcinoma (PDAC). Inactivation of HS3ST1, a key enzyme in HSAT synthesis, in PDAC cells eliminated HSAT expression, induced an inflammatory phenotype, suppressed markers of apoptosis, and increased metastasis in an experimental mouse PDAC model. HSAT-positive PDAC cells bind AT, which inhibits the generation of active thrombin by tissue factor (TF) and Factor VIIa. Furthermore, plasma from PDAC patients showed accumulation of HSAT suggesting its potential as a marker of tumor formation. These findings suggest that HSAT exerts a tumor suppressing function through recruitment of AT and that the decrease in HSAT during progression of pancreatic tumorigenesis increases inflammation and metastatic potential.

Graphical Abstract
graphical abstract
Supplemental material

View

View Full unedited western blots

Version history
  • Version 1 (September 16, 2025): In-Press Preview
Advertisement
Advertisement