Abstract

Several angiogenesis-promoting factors have prognostic significance in ovarian cancer. The objective of this study was to evaluate whether traditional chemotherapy affects angiogenesis-related factors in ovarian carcinoma and to assess the clinical significance of these effects. To screen for angiogenesis-related factors of possible relevance, OVCAR-3 and A2780 ovarian cancer cells were treated with IC(50) doses of cisplatin (CDDP) or docetaxel, or with bevacizumab, and mRNA expression of several angiogenesis-related factors was analyzed. Thrombospondin-1 (TSP-1), bone morphogenetic protein-4 (BMP-4), endothelin-1, and placental growth factor-2 were statistically significantly induced by CDDP. At protein level, CDDP also induced hypoxia-inducible factor-1α but not vascular endothelial growth factor. In carcinoma samples taken before and after platinum-based neoadjuvant chemotherapy from 28 patients with advanced, high-grade serous ovarian carcinoma, CD105 and factors most induced by CDDP (TSP-1 and BMP-4) were analyzed by immunohistochemistry. Strong expression of BMP-4 before chemotherapy was an independent prognostic factor of longer progression-free time (p = 0.002) and overall survival (p = 0.02), but it was not associated with neovascularization (as evaluated by CD105). However, changes in BMP-4 expression in samples analyzed before and after chemotherapy (observed in 22/28 patients) were not associated with prognosis. TSP-1 expression was not associated with clinical parameters. Our results indicate that in serous ovarian carcinoma, BMP-4 has prognostic significance, which is not angiogenesis-related. We also show that CDDP induces several angiogenesis-related growth factors in vitro and future studies are warranted to clarify the clinical significance of this phenomenon.