Erythropoeitin receptor function and expression in epithelial ovarian carcinoma

Abstract

Our objectives were to determine if the erythropoietin receptor (EpoR) has increased expression in epithelial ovarian carcinoma, and if erythropoietin (Epo) confers malignant properties to ovarian cancer cell lines. A Western blot analysis of protein lysates from normal ovarian surface epithelial cells and ovarian cancer cell lines was performed. In addition, immunohistochemical (IHC) staining for EpoR in tissue specimens of normal, low malignant potential tumor, and epithelial ovarian carcinoma was performed. Epo effect on ovarian cancer cell lines was investigated by a cytotoxicity assay using a cell line with high (OVCAR3) and low (SKOV3) EpoR expression. Western blot analysis revealed increased expression of EpoR in multiple ovarian cancer cell lines. IHC staining revealed limited EpoR expression in benign ovarian tissue and increased levels in ovarian low malignant potential (LMP) tumor and carcinoma. This difference between benign ovarian tissue and carcinoma was found to be statistically significant using a quantitative scoring system. In addition, a cytotoxicity assay with paclitaxel and cisplatin revealed an attenuation of cytotoxic effects. Increased EpoR expression in ovarian LMP tumors and carcinoma is demonstrated by Western blot analysis and IHC staining. Furthermore, adversely effects sensitivity to cisplatin in the ovarian cancer cell lines. These data add to the growing body of evidence suggesting possible detrimental effects of erythropoietin.