In vitro interactions between mammary fibroblasts (Hs 578Bst) and cancer epithelial cells (MCF-7) modulate aromatase, steroid sulfatase and 17β-hydroxysteroid dehydrogenases.

Mol Cell Endocrinol

Research Center of the CHU de Québec, CHUL, 2705, Boulevard Laurier, Quebec City, G1V 4G2, Canada; Department of Surgery, Faculty of Medicine, Laval University, 1050, Avenue de la Médecine, Quebec City, G1V OA6, Canada. Electronic address:

Published: September 2015

Our objectives were to investigate the interactions between mammary cancer epithelial cells (MCF-7) and stromal cells (Hs-578Bst) at the level of the expression and inhibition of steroidogenesis enzymes by using monolayer and three dimensional co-culture models. Expressions of steroidogenesis enzymes and E2/DHT conversions in co-cultured MCF-7 and Hs-578Bst cells as well as the effects of aromatase inhibitor combined to steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenases (17βHSDs) inhibitors were evaluated. 17β-HSD type 7 was mostly modulated in MCF-7 cells whereas aromatase was mostly regulated in Hs578Bst cells thereby increasing E2 conversion and MCF-7 cell growth. A combination of inhibitors toward aromatase, STS and 17β-HSD7, was found to be the most significant treatment in decreasing E2 and elevating DHT thus inhibiting MCF-7 cell proliferation and spheroid-like cancer cell aggregation in collagen gel. The interactions between those cells modulated E2 formation in paracrine/intracrine manners by synergistically regulating aromatase, 17β-HSD7 and STS. Among tumor-associated cells, stromal fibroblasts may participate in intratumoral E2 deposition; therefore promoting breast cancer cell growth.

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http://dx.doi.org/10.1016/j.mce.2015.05.032DOI Listing

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