title: In vitro interactions between mammary fibroblasts (Hs 578Bst) and cancer epithelial cells (MCF-7) modulate aromatase, steroid sulfatase and 17β-hydroxysteroid dehydrogenases.
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.
authors.affiliation: Research Center of the CHU de Québec, CHUL, 2705, Boulevard Laurier, Quebec City, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050, Avenue de la Médecine, Quebec City, G1V OA6, Canada.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Research Center of the CHU de Québec, CHUL, 2705, Boulevard Laurier, Quebec City, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050, Avenue de la Médecine, Quebec City, G1V OA6, Canada.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Sang
authors.affiliation: Centre des Maladie du Sein Deschênes-Fabia, Hôpital du Saint-Sacrement, 1050, Chemin Sainte-Foy, Quebec City, G1S 4L8, Canada; Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, 1050, Avenue de la Médecine, Quebec City, G1V OA6, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Diorio
authors.affiliation: Research Center of the CHU de Québec, CHUL, 2705, Boulevard Laurier, Quebec City, G1V 4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Laval University, 1050, Avenue de la Médecine, Quebec City, G1V OA6, Canada.
authors.forename: Sheng-Xiang
authors.initials: SX
authors.lastname: Lin
authors.affiliation: 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: charles.doillon@crchul.ulaval.ca.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Doillon
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000473:pathology; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D043266:Steryl-Sulfatase
keywords: 17β Hydroxysteroid dehydrogenases; 3D cell co-cultures; Aromatase; Cell–cell interactions; Estrogen-dependent breast cancer; Steroidogenesis enzymes