Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment
Puneeth Iyengar, … , Paolo Bonaldo, Philipp E. Scherer
Puneeth Iyengar, … , Paolo Bonaldo, Philipp E. Scherer
Published May 2, 2005
Citation Information: J Clin Invest. 2005;115(5):1163-1176. https://doi.org/10.1172/JCI23424.
View: Text | PDF
Article Oncology Article has an altmetric score of 4

Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment

  • Text
  • PDF
Abstract

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen–/– mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and β-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIα3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.

Authors

Puneeth Iyengar, Virginia Espina, Terence W. Williams, Ying Lin, David Berry, Linda A. Jelicks, Hyangkyu Lee, Karla Temple, Reed Graves, Jeffrey Pollard, Neeru Chopra, Robert G. Russell, Ram Sasisekharan, Bruce J. Trock, Marc Lippman, Valerie S. Calvert, Emanuel F. Petricoin III, Lance Liotta, Ekaterina Dadachova, Richard G. Pestell, Michael P. Lisanti, Paolo Bonaldo, Philipp E. Scherer

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Breast tumor cell protein expression and activation differences between ...
Breast tumor cell protein expression and activation differences between collagen VI+/+ and collagen VI–/– mice in the background of the MMTV-PyMT transgene. (A) Laser-capture microdissection was used to isolate hyperplastic cells in a 100-μM radius from adipocytes. A representative example is shown in the top panels, before (panel 1) and after (panel 2) removal of cells. Similarly, cells not associated at all with adipocytes (> 500 μM from the nearest adipocyte) were isolated from pathologically matched sections from mice carrying the MMTV-PyMT transgene in either a collagen VI+/+ or a collagen VI–/– background (panels 3 and 4). Arrows indicate the targeted areas before and after isolation of cells. (B) Material from at least 8 independent areas was pooled in each case and analyzed. The material was used to make protein extracts that were spotted on protein arrays. The results shown were obtained from arrays of cells in close proximity to adipocytes. Arrays were probed with various antibodies against total and activated forms of proteins implicated in pro-oncogenic pathways. *P < 0.05. (C) Quantitative comparison of the ratio of phospho-specific protein to total protein from arrays used in B. Results are shown as mean ± SEM. *P < 0.05.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 1 X users
Referenced in 6 patents
229 readers on Mendeley
See more details