Tumor microvasculature with endothelial fenestrations in VHL null clear cell renal cell carcinomas as a potent target of anti-angiogenic therapy.

ABSTRACT: Vascular endothelial growth factor (VEGF)-targeted therapies show significant antitumor effects for advanced clear cell renal cell carcinomas (CC-RCCs). Previous studies using VEGF inhibitors in mice models revealed that VEGF-dependent capillaries were characterized by the existence of endothelial fenestrations (EFs). In this study, we revealed that capillaries with abundant EFs did exist, particularly in CC-RCCs harboring VHL mutation. This finding was recapitulated in mice xenograft models, in which tumors from VHL null cells showed more abundant EFs compared to those from VHL wild-type cells. Importantly, treatment with bevacizumab resulted in a significant decrease of tumor size established from VHL null cells. Additionally, a significant reduction of EFs and microvessel density was ob

SUBMITTER: Yamasaki T 

PROVIDER: S-EPMC7659343 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature