The unique role of VEGF in renal cell carcinoma (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.¹

Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043. Reprinted with permission from the American Society of Clinical Oncology.

Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis.^1,2 VEGF is highly expressed in many human cancers, but renal cell carcinoma (RCC) in particular produces remarkably high levels, with tumors having a highly vascular histologic appearance. The high VEGF expression 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.^1,3

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).⁴ 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.^1-3,5

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.⁶

References:

1.

Rini BI, Small EJ. J Clin Oncol. 2005;23:1028-1043.

2.

Jacobsen J, Grankvist K, Rasmuson T, Bergh A, Landberg G, Ljungberg B. BJU Int. 2004;93:297-302.

3.

Haase VH. Kidney Int. 2006;69:1302-1307.

4.

George DJ, Kaelin WG Jr. N Engl J Med. 2003;349:419-421.

5.

Yildiz E, Gokce G, Kilicarslan H, Ayan S, Goze OF, Gultekin EY. BJU Int. 2004;93:1087-1093.

6.

Tsuchiya N, Sato K, Akao T, et al. Tohoku J Exp Med. 2001;195:101-113.