Abstract

Abstract 27 Ovarian cancer is the first cause of death for gynecological malignances in developed 28 countries and around 80% correspond to Epithelial Ovarian Cancer (EOC). 29 Overexpression of Nerve Growth Factor (NGF) and its high affinity receptor TRKA are 30 involved in EOC progression, modulating several oncogenic processes such as 31 angiogenesis by the increase of Vascular Endothelial Growth Factor (VEGF). FSH 32 receptors (FSH-R) are present in EOC, but their changes and contribution during EOC 33 progression are still not thoroughly known. The aims of this study were to evaluate the 34 abundance of FSH receptors during EOC differentiation and to determine whether FSH 35 modulates oncoproteins such as NGF and VEGF in ovarian cells. FSH-R expression in 36 EOC tissues and cell lines (A2780, poorly differentiated EOC cells and HOSE, non37 tumoral ovarian surface epithelial cells) were measured by RT-PCR and laser capture of 38 epithelial cells from EOC samples by qPCR. FSH-R protein levels were evaluated by 39 immunohisto/cytochemistry. Additionally, ovarian explants and ovarian cell lines were 40 stimulated with FSH and/or FSH-R inhibitor to assess NGF and VEGF mRNA and 41 protein levels. 42 The results showed that FSH-R levels decreased during EOC progression, nevertheless 43 these receptors are still present in poorly differentiated EOC. FSH increased NGF 44 expression in ovarian cells, which was prevented using a FSH-R inhibitor. Similarly, in 45 ovarian cancer explants, FSH increased NGF and VEGF mRNA, as well as NGF 46 protein levels. These results suggest that FSH would display a key role not only in 47 initial stages of EOC, but also in late stages of this disease, by modulation of NGF and 48 VEGF levels in EOC cells.