Follicle-stimulating hormone promotes nerve growth factor and vascular endothelial growth factor expression in epithelial ovarian cells
Maritza P. Garrido1,2, Nicole Bruneau2, Margarita Vega1,2, Alberto Selman2,3, Julio C. Tapia4 and Carmen Romero1,2
1Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital University of Chile, 2Department of Obstetrics and Gynecology, Faculty of Medicine, University of Chile, 3National Institute of Cancer and 4Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile
Offprint requests to: Carmen Romero, Laboratory of Endocrinology and Reproduction Biology, Clinical Hospital, University of Chile, Department of Obstetrics and Gynecology, Faculty of Medicine, Clinical Hospital University of Chile, Santos Dumont # 999, Santiago, Chile. e-mail: cromero@hcuch.cl
Summary. Ovarian cancer is the first cause of death for gynecological malignances in developed countries and around 80% correspond to Epithelial Ovarian Cancer (EOC). Overexpression of Nerve Growth Factor (NGF) and its high affinity receptor TRKA are involved in EOC progression, modulating several oncogenic processes such as angiogenesis by the increase of Vascular Endothelial Growth Factor (VEGF). FSH receptors (FSH-R) are present in EOC, but their changes and contribution during EOC progression are still not thoroughly known. The aims of this study were to evaluate the abundance of FSH receptors during EOC differentiation and to determine whether FSH modulates oncoproteins such as NGF and VEGF in ovarian cells. FSH-R expression in EOC tissues and cell lines (A2780, poorly differentiated EOC cells and HOSE, non-tumoral ovarian surface epithelial cells) were measured by RT-PCR and laser capture of epithelial cells from EOC samples by qPCR. FSH-R protein levels were evaluated by immunohisto/cytochemistry. Additionally, ovarian explants and ovarian cell lines were stimulated with FSH and/or FSH-R inhibitor to assess NGF and VEGF mRNA and protein levels.
The results showed that FSH-R levels decreased during loss of EOC cell differentiation, nevertheless these receptors are still present in poorly differentiated EOC. FSH increased NGF expression in ovarian cells, which was prevented using a FSH-R inhibitor. Similarly, in ovarian cancer explants, FSH increased NGF and VEGF mRNA, as well as NGF protein levels. These results suggest that FSH would display a key role not only in initial stages of EOC, but also in late stages of this disease, by modulation of NGF and VEGF levels in EOC cells. Histol Histopathol 35, 961-971 (2020)
Key words: Epithelial Ovarian Cancer, NGF, FSH, LH, VEGF
DOI: 10.14670/HH-18-226