The Proangiogenic Capabilities of Malignant Ascites Generated by Aggressive Ovarian Tumors

Abstract

Here we examined whether malignant ascites may determine ovarian tumor angiogenesis, and if so whether ascites generated by highly aggressive serous and undifferentiated cancers are more proangiogenic than those from less aggressive clear cell and endometrioid tumors. Angiogenesis was analyzed according to expression of CD31, CD34, and connexin 43. Proliferation and migration of endothelial cells were tested using fluorescence-based methods. The quantification of angiogenic agents and hypoxia-inducible factor 1α (HIF-1α) was performed using specific immunoassays. Results showed that the expression of CD31 and CD34 in serous and undifferentiated tumors was greater, whereas endothelial expression of connexin 43 was lower than in clear cell and endometrioid lesions. Serous cancers that formed in the presence of ascites displayed increased expression of connexin 43 in vascular smooth muscles as compared with tumors developed in the fluid's absence. Endothelial cells exposed to ascites from serous and undifferentiated tumors proliferated and migrated more vigorously than cells subjected to ascites from clear cell and endometrioid cancers. They also exhibited an increased level of HIF-1α and produced increased amounts of multiple proangiogenic agents. Our results indicate that high vascularization of aggressive ovarian tumors may be associated with profound angiogenic capabilities of ascites generated by these tumors.