title: Supernatants of Adipocytes From Obese Versus Normal Weight Women and Breast Cancer Cells: In Vitro Impact on Angiogenesis.
abstract: Breast cancer is correlated with a higher risk of metastasis in obese postmenopausal women. Adipokines, whose plasma concentrations are modulated in obese subjects and adipocytes surround mammary cells, suggesting that adipocyte secretome affect mammary tumorogenesis. We hypothesize that mature adipocyte secretions from obese women conditioned or not by breast neoplasic cells, increase changes on the angiogenesis stages. Supernatants of human mature adipocytes, differentiated from stem cells of either adipose tissue of normal weight (MA20) or obese (MA30) women or obtained from co-cultures between MA20 and MA30 and breast cancer cell line MCF-7, were collected. The impact of these supernatants was investigated on proliferation, migration, and tube formation by endothelial cells (HUVEC). MA20 and MA30 showed a preservation of their "metabolic memory" (increase of Leptin, ObR, VEGF, CYP19A1, and a decrease of Adiponectin expression in MA30 compared to MA20). Supernatants from obese-adipocytes increased HUVEC proliferation, migration, and sprouting like with supernatants obtained from co-cultures of MA/MCF-7 regardless the women's BMI. Additional analyses such as the use of neutralizing antibodies, analysis of supernatants (Milliplex®) and variations in gene expression (qRT-PCR), strongly suggest an implication of IL-6, or a synergistic action among adipokines, probably associated with that of VEGF or IL-6. As a conclusion, supernatants from co-cultures of MA30 and MCF-7 cells increase proliferation, migration, and sprouting of HUVEC cells. These results provide insights into the interaction between adipocytes and epithelial cancer cells, particularly in case of obesity. The identification of synergistic action of adipokines would therefore be a great interest in developing preventive strategies. J. Cell. Physiol. 232: 1808-1816, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Bougaret
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Delort
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Hermine
authors.initials: H
authors.lastname: Billard
authors.affiliation: Banque de Tissus et de Cellules, Lyon, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lequeux
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goncalves-Mendes
authors.affiliation: Service de Chirurgie Plastique, Reconstructrice et Esthétique, Hôpital Edouard-Herriot, Lyon, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Mojallal
authors.affiliation: Banque de Tissus et de Cellules, Lyon, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Damour
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.|Centre Anti-Cancéreux Jean-Perrin, Clermont-Ferrand, France.|Cancéropôle Lyon Auvergne Rhône-Alpes (CLARA), Lyon, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Vasson
authors.affiliation: UMR1019-INRA-UdA, Unité de Nutrition Humaine, Equipe ECREIN, UFR Pharmacie, Université d'Auvergne, Clermont-Ferrand, France.|Cancéropôle Lyon Auvergne Rhône-Alpes (CLARA), Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Caldefie-Chezet
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000273:Adipose Tissue / Q000473:pathology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009765:Obesity / Q000473:pathology*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D017077:Culture Media, Conditioned; D054411:Receptors, Leptin; D040301:Vascular Endothelial Growth Factor Receptor-2