ScienceVEGF

The multiple roles of VEGF throughout the development of ovarian cancer

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VEGF overexpression mediates a number of important developments in ovarian cancer tumourigenesis and proliferation.^2,5

 

As in other cancers, angiogenesis is crucial for ovarian tumour growth.⁵ VEGF is associated with the promotion of angiogenesis in early-stage ovarian cancer, implicating VEGF-induced angiogenesis as an early contributor in ovarian carcinogenesis.¹ Additionally, preclinical studies have shown that VEGF-A overexpression in surface epithelium can transform normal, functional ovarian epithelium into ascites-producing cancers.^2,11

 

Ovarian carcinomas tend to produce vasculature that is structurally and functionally abnormal: vessels are characteristically leaky and immature, and provide poor flow overall.⁵ VEGF has been shown to enhance vessel permeability, and in one study, it regulated the permeability of peritoneal vessels that lead to ascites development.^2,8,12 This is consistent with the findings of Belotti et al. that provided direct preclinical evidence that pathways involving the release of VEGF contribute to the formation of ascites through pathways involving MMP9 (and, to a lesser extent, MMP2).¹⁰

 

Interestingly, VEGF may also serve as an important survival factor for endothelial cells experiencing chemical or physical stress.¹¹ In one ovarian cancer model, cells treated with a chemotherapeutic agent induced a significant increase in VEGF expression that appeared to contribute to cell survival.¹³ In another preclinical study, exogenous overexpression of VEGF has also been shown to reduce chemotherapeutic-induced apoptosis.⁸