ALBERT

Description: ABSTRACT Breast cancer is correlated with a higher risk of metastasis in obese postmenopausal women. Adipokines, whose plasma concentrations are modulated in obese subjects, surrounds mammary cells, suggesting that adipocyte secretions affect mammary tumorogenesis. We hypothsesis that matures adipocytes secretions from obese women conditioned or not by breast neoplasic cells, increase changes on the stages of angiogenesis. Supernatants of human matures adipocytes differentiated from stem cells of either adipose tissue of normal weight (MA20) or obese (MA30) women or obtained from co-cultures between MA20 or MA30 and breast cancer cell line MCF-7 were collected. The impact of these supernatants was investigated on proliferation, migration and tubes formation by endothelial cells (HUVEC). MA20 and MA30 showed a preservation of their “metabolic memory” (increase of Leptin , ObR, VEGF , CYP19A1 and decrease of Adiponectin expressions in MA30 compared to MA20). Supernatant from obese-adipocytes increased HUVEC proliferation, migration and sprouting like with supernatant 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, supernatant 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. This article is protected by copyright. All rights reserved