Article ID Journal Published Year Pages File Type
8476995 Molecular and Cellular Endocrinology 2015 27 Pages PDF
Abstract
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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