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Updated: Jul 11, 2026
Isolation and Culture Expansion of Tumor-specific Endothelial Cells
Published on: October 14, 2015
Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern
Alexandra Abramsson1, Per Lindblom, Christer Betsholtz
1Department of Medical Biochemistry, Sahlgrenska Academy at Göteberg University, Göteborg, Sweden.
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-Rbeta in pericyte recruitment in a mouse fibrosarcoma model. In tumors transplanted into PDGF-B retention motif-deficient (pdgf-b(ret/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-b(ret/ret) mice but failed to correct the pericyte detachment in pdgf-b(ret/ret) mice. Coinjection of exogenous pericytes and tumor cells showed that pericytes require PDGF-Rbeta 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-Rbeta as promising molecular targets for therapeutic intervention.
Insights
Targeting pericytes, crucial for tumor blood vessel integrity, offers new therapeutic avenues. Platelet-derived growth factor B (PDGF-B) and PDGF receptor beta (PDGF-Rbeta) are key molecular targets for enhancing pericyte function in tumors.
Area of Science:
- Oncology
- Vascular Biology
- Molecular Biology
Background:
- Tumor blood vessels exhibit abnormal morphology and biochemistry, distinct from normal vasculature.
- Current anti-angiogenic therapies primarily target endothelial cells, but pericyte-targeted approaches may offer additional benefits.
- Understanding pericyte recruitment and function in tumors is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the roles of Platelet-Derived Growth Factor B (PDGF-B) and PDGF receptor beta (PDGF-Rbeta) in pericyte recruitment within a mouse fibrosarcoma model.
- To elucidate the specific functions of PDGF-B and PDGF-Rbeta in pericyte-endothelial cell interactions and vessel stabilization.
Main Methods:
- Utilized genetic tools, including PDGF-B retention motif-deficient (pdgf-b(ret/ret)) mice and transgenic PDGF-B expression.
- Assessed pericyte density, vessel morphology (diameter), and vessel integrity (hemorrhaging) in transplanted tumors.
- Employed co-injection of tumor cells and exogenous pericytes to study recruitment mechanisms.
Main Results:
- Tumors in pdgf-b(ret/ret) mice showed reduced pericyte density, partial pericyte detachment, increased vessel diameter, and hemorrhaging.
- Tumor cell-derived PDGF-B increased pericyte density but did not correct pericyte detachment in pdgf-b(ret/ret) mice.
- Pericyte recruitment to tumor vessels requires PDGF-Rbeta, while endothelial PDGF-B retention is essential for pericyte integration into the vessel wall.
Conclusions:
- Pericytes play a significant role in maintaining the integrity of tumor vasculature.
- PDGF-B and PDGF-Rbeta are critical regulators of pericyte recruitment and function in tumors.
- These findings highlight PDGF-B and PDGF-Rbeta as promising molecular targets for anti-cancer therapies aimed at normalizing tumor vasculature.
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