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Contrasting effects of VEGF gene disruption in embryonic stem cell-derived versus oncogene-induced tumors

Alicia Viloria-Petit1, Lucile Miquerol, Joanne L Yu

  • 1Molecular and Cellular Biology Research, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Ontario M4N 3M5, Canada.

The EMBO Journal
|August 13, 2003
PubMed

Insights

Tumor cells lacking vascular endothelial growth factor (VEGF) can still form aggressive tumors. Blocking other pathways, like thrombospondin 1 (TSP-1), can inhibit tumor growth, suggesting alternative anti-angiogenesis strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Vascular Endothelial Growth Factor (VEGF) is crucial for tumor angiogenesis, especially in embryonal or endocrine tumors.
  • Previous studies suggested VEGF is essential for tumor blood vessel formation.

Purpose of the Study:

  • To investigate the role of tumor cell-derived VEGF in adult fibrosarcoma angiogenesis.
  • To explore VEGF-independent pathways in tumor angiogenesis and potential therapeutic targets.

Main Methods:

  • Generated VEGF-deficient fibrosarcomas using oncogene-transformed adult fibroblasts and embryonic stem cells.
  • Analyzed the expression of angiogenesis inhibitors (PEDF, TSP-1) in VEGF-null tumors.
  • Administered a TSP-1 peptide (ABT-526) to assess its effect on tumor growth.

Main Results:

  • VEGF-deficient fibroblasts transformed with ras or neu oncogenes formed highly tumorigenic and angiogenic fibrosarcomas.
  • Tumorigenic deficiency of VEGF(-/-) embryonic stem cells contrasted with the aggressive nature of derived tumors.
  • Oncogenes downregulated endogenous angiogenesis inhibitors PEDF and TSP-1.
  • Treatment with an anti-TSP-1 peptide (ABT-526) significantly inhibited tumor growth.

Conclusions:

  • Tumor cell-derived VEGF is dispensable for angiogenesis in certain adult tumors.
  • VEGF-independent pathways contribute to tumor angiogenesis.
  • Targeting both VEGF-dependent and independent pathways may be necessary for effective anti-angiogenesis therapy.

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