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Updated: Aug 23, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis
Jianying Dong1, Jeremy Grunstein, Max Tejada
1Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
Abstract:
We generated VEGF-null fibrosarcomas from VEGF-loxP mouse embryonic fibroblasts to investigate the mechanisms of tumor escape after VEGF inactivation. These cells were found to be tumorigenic and angiogenic in vivo in spite of the absence of tumor-derived VEGF. However, VEGF derived from host stroma was readily detected in the tumor mass and treatment with a newly developed anti-VEGF monoclonal antibody substantially inhibited tumor growth. The functional significance of stroma-derived VEGF indicates that the recruitment of stromal cells is critical for the angiogenic and tumorigenic properties of these cells. Here we identified PDGF AA as the major stromal fibroblast chemotactic factor produced by tumor cells, and demonstrated that disrupting the paracrine PDGFR alpha signaling between tumor cells and stromal fibroblasts by soluble PDGFR alpha-IgG significantly reduced tumor growth. Thus, PDGFR alpha signaling is required for the recruitment of VEGF-producing stromal fibroblasts for tumor angiogenesis and growth. Our findings highlight a novel aspect of PDGFR alpha signaling in tumorigenesis.
Insights
Tumor cells can evade Vascular Endothelial Growth Factor (VEGF) inactivation by recruiting stromal cells. Platelet-Derived Growth Factor AA (PDGF AA) signaling drives this recruitment, which is essential for tumor growth and angiogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor growth and angiogenesis are often dependent on Vascular Endothelial Growth Factor (VEGF).
- Mechanisms of tumor escape following VEGF inactivation are not fully understood.
- Tumor cells can utilize VEGF from host stroma for growth.
Purpose of the Study:
- To investigate tumor escape mechanisms after VEGF inactivation.
- To identify signaling pathways involved in recruiting VEGF-producing stromal cells.
- To explore the role of Platelet-Derived Growth Factor Alpha (PDGFR alpha) signaling in tumorigenesis.
Main Methods:
- Generation of VEGF-null fibrosarcomas from mouse embryonic fibroblasts.
- In vivo tumor growth and angiogenesis assays.
- Treatment with anti-VEGF monoclonal antibody and soluble PDGFR alpha-IgG.
- Identification of chemotactic factors using molecular assays.
Main Results:
- VEGF-null fibrosarcomas remained tumorigenic and angiogenic, utilizing host stromal VEGF.
- Anti-VEGF antibody treatment inhibited tumor growth.
- Platelet-Derived Growth Factor AA (PDGF AA) was identified as a key chemotactic factor for stromal fibroblasts.
- Disruption of PDGFR alpha signaling significantly reduced tumor growth.
Conclusions:
- Tumor cells can escape VEGF inactivation by recruiting stromal cells.
- PDGF AA-mediated PDGFR alpha signaling is crucial for recruiting VEGF-producing stromal fibroblasts.
- Targeting PDGFR alpha signaling represents a potential therapeutic strategy for inhibiting tumor angiogenesis and growth.
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