The unique role of VEGF in RCC pathogenesis
Effects of VEGF in RCC
VEGF is a key mediator of angiogenesis in RCC. Downstream effects of VEGF include increased survival, migration and proliferation of endothelial cells.2
Rini BI, Small EJ. J Clin Oncol 2005;23:1028–43. Reprinted with permission from the American Society of Clinical Oncology.
VEGF is a potent inducer of tumour angiogenesis.2,8 VEGF is expressed in many human cancers, but RCC in particular produces remarkably high levels, with tumours having a highly vascular histological appearance. The overexpression of VEGF in RCC is the direct result of inactivation of VHL gene. Data suggest that VHL inactivation occurs in the majority of clear-cell RCCs.2,4
Loss of pVHL expression results in constitutive expression of HIF-1α and induction of hypoxia-regulated genes, including those encoding for VEGF, PDGF-β and TGF-α.3 These gene products have been implicated in the malignant phenotype of RCC, which is characterised by hypervascular tumours, local and distant metastases via haematogenous 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, VEGFR expression has been observed in RCC cells, suggesting that VEGF may also serve as an autocrine stimulus in RCC.10
- Disclaimer: Avastin.net is a comprehensive resource for healthcare professionals outside the US. If you are a US resident please visit www.avastin.comThe information on this site is not country-specific and may contain information that is outside the approved indications in the country in which you are located.