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.

Clinicopathologic factors associated with short-term survival in advanced epithelial ovarian cancer

“…Recent data indicated that a large amount of ascites at the initial diagnosis of EOC was associated with worse prognosis, which may be related in part to decreased possibility of performing complete tumor resection as well ( 17 ). Additionally, ascites volume strongly promotes angiogenesis and increases cancer cells’ transmesothelial invasion ( 18 , 19 ), and a more interesting finding was that the expression of multidrug resistance associated protein in ovarian cancer cells was caused by increased ascites volume ( 20 ), but exact mechanism is yet unclear. Our results demonstrate the median of ascites volume in STS was 700 mL compared to that of LTS, which was 300 mL, but there is no significant difference, and we need to include more patients to explore the impact of ascitic fluid volume on survival.…”

The Epithelial-Mesenchymal Transition Initiated by Malignant Ascites Underlies the Transmesothelial Invasion of Ovarian Cancer Cells

“…This term refers to pathologic fluid that accumulates in the abdomen in a group of patients, mostly in the advanced stages of the disease [2]. Malignant ascites have been found to create hospitable conditions for tumor expansion by suppressing peritoneal inflammatory reactions [3], inducing angiogenesis [4], and promoting cancer cell proliferation [5] and migration [6].…”

Relationship between ascites volume and clinical outcomes in epithelial ovarian cancer

“…Extensive evidence supports the critical role of VEGF in ascites formation and ovarian cancer progression and recurrence. Components of ascites are known to have potent angiogenic capabilities, and such components promote hypervascularization of aggressive tumors 31 . Some studies had shown that the combination of anti‐angiogenic agents such as bevacizumab with standard chemotherapy would improve PFS and OS for the patients with ascites 32 .…”