Local estrogen metabolism in epithelial ovarian cancer suggests novel targets for therapy

[Display omitted] •Human ovarian surface epithelium (OSE) and epithelial ovarian cancer (EOC) cells have the capacity for local metabolism of estrogen.•Estrogen is differentially metabolized in OSE and EOC cells, with E2 formation from conjugated estrogen predominating in cancer cells.•Inflammatory cytokines augment the local production of E2 by stimulating steroid sulfatase and suppressing estrogen sulfotransferase.•STS inhibition and/or EST augmentation (local estrogen metabolism) show promise as a target for EOC treatment. Epithelial ovarian cancer (EOC) accounts for about 90% of malignant ovarian tumors, and estrogen is often implicated in disease progression. We therefore compared the potential for gating of estrogen action via pre-receptor metabolism in normal human ovarian surface epithelium (OSE), EOC and selected EOC cell lines (SKOV3 and PEO1). Steroid sulphatase (STS), estrogen sulfotransferase (EST), 17β-hydroxysteroid dehydrogenases 2 (17BHSD2) and 5 (17BHSD5) mRNAs, proteins and enzymatic activities were all detectable in primary cell cultures of OSE and EOC, whereas aromatase and 17BHSD1 expression was negligible. qRT-PCR assay on total mRNA revealed significantly higher EST mRNA expression in OSE compared to EOC (P