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Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis.2,8 VEGF is overexpressed in many human cancers, but renal cell carcinoma (RCC) in particular produces remarkably high levels, with tumors having a highly vascular histologic appearance. The overexpression of VEGF in RCC is the direct result of inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Data suggest that VHL inactivation occurs in the majority of clear-cell RCCs.2,4
Loss of VHL protein (pVHL) expression results in constitutive expression of HIF-1α and induction of hypoxia-regulated genes, including those encoding for VEGF, platelet-derived growth factor-β (PDGF-β), and transforming growth factor-α (TGF-α).3 These gene products have been implicated in the malignant phenotype of RCC, which is characterized by hypervascular tumors, local and distant metastases via hematogenous spread, uncontrolled growth, and resistance to apoptosis.2,4,8,9
The role of VEGF in particular has been explored as a key factor in the pathogenesis of RCC. VEGF functions to increase vascular permeability, induce endothelial cell proliferation and migration, and promote endothelial cell survival. Thus, VEGF serves as a potent promoter of angiogenesis.2 Furthermore, VEGF receptor expression has been observed in RCC cells, suggesting that VEGF may also serve as an autocrine stimulus in RCC.10
