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 ...
    • Pancreatic Cancer (Jul 2025)
    • 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)
    • 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
Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors
Alexandra Abramsson, … , Per Lindblom, Christer Betsholtz
Alexandra Abramsson, … , Per Lindblom, Christer Betsholtz
Published October 15, 2003
Citation Information: J Clin Invest. 2003;112(8):1142-1151. https://doi.org/10.1172/JCI18549.
View: Text | PDF
Article Oncology

Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors

  • Text
  • PDF
Abstract

Tumor-infiltrating blood vessels deviate morphologically and biochemically from normal vessels, raising the prospect of selective pharmacological targeting. Current antiangiogenic approaches focus mainly on endothelial cells, but recent data imply that targeting pericytes may provide additional benefits. Further development of these concepts will require deeper insight into mechanisms of pericyte recruitment and function in tumors. Here, we applied genetic tools to decipher the function of PDGF-B and PDGF-Rβ in pericyte recruitment in a mouse fibrosarcoma model. In tumors transplanted into PDGF-B retention motif–deficient (pdgf-bret/ret) mice, pericytes were fewer and were partially detached from the vessel wall, coinciding with increased tumor vessel diameter and hemorrhaging. Transgenic PDGF-B expression in tumor cells was able to increase the pericyte density in both WT and pdgf-bret/ret mice but failed to correct the pericyte detachment in pdgf-bret/ret mice. Coinjection of exogenous pericytes and tumor cells showed that pericytes require PDGF-Rβ for recruitment to tumor vessels, whereas endothelial PDGF-B retention is indispensable for proper integration of pericytes in the vessel wall. Our data support the notion that pericytes serve an important function in tumor vessels and highlight PDGF-B and PDGF-Rβ as promising molecular targets for therapeutic intervention.

Authors

Alexandra Abramsson, Per Lindblom, Christer Betsholtz

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Exogenous PDGF-Rβ–deficient pericytes are not recruited by tumor vessels...
Exogenous PDGF-Rβ–deficient pericytes are not recruited by tumor vessels. MEFs were isolated from XlacZ4-positive WT or PDGF-Rβ–negative embryonic day 12.5 embryos and cultured in vitro (a and b). These cultures contained similar proportions of XlacZ4-positive cells (∼10%). T241 cells mixed with MEFs at a 1:9 ratio were injected subcutaneously onto the backs of WT mice. Cells expressing lacZ (pink) were found closely associated with endothelial cells (Pecam-1, brown) in tumors mixed with PDGF-Rβ–positive MEF cells (c, arrows) but not in tumors mixed with PDGF-Rβ–negative MEF cells (d). Triple staining shows that the recruited lacZ-positive MEF cells (e, arrowheads) also express SMA (green) and that the lacZ/SMA double-positive cells are tightly associated with the endothelium (brown) (e). Vessels in tumors mixed with PDGF-Rβ–negative MEF cells lack exogenous (lacZ-positive) pericytes but recruit endogenous (lacZ-negative, SMA-positive) pericytes, as expected (f, arrows). Prelabeling of MEF cultures with Pkh26 dye indicates the presence and similar distribution of PDGF-Rβ–positive and –negative MEF cells within the tumors (g and h). Bars: 100 μm (a and b), 50 μm (c, d, g, and h), and 20 μm (e and f).

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

Sign up for email alerts