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.

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

“…interestingly, with the decrease of the donors' BMi, the proliferation activity of the corresponding das decreased compared with adScs. This tendency was consistent with clinical experience, that is, the survival rate of fat transplantation in obese patients is relatively higher compared with lean individuals, which may be associated with the higher activity of MAs, although the specific mechanism is yet to be elucidated (30). due to the limited number of cases in the present study, this result may also be caused by factors such as different donor site locations, thus further experiments are required to clarify this hypothesis.…”

Cancer-associated adipocytes: emerging supporters in breast cancer

“…In addition, co-culture of adipocytes and BC cells increased the secretion of VEGF and leptin, and thus enhanced the effects of estradiol and altered the risk of BC [ 60 ]. Co-cultured supernatants of adipocytes could also increase the proliferation, migration and sprouting of human umbilical vein endothelial cells (HUVECs), which might be ascribed to angiogenesis-associated VEGF [ 61 ]. Adipocytes, coupled with adipose-derived stem cells (ADSCs), are the main producers of ATX and LPA, which have attracted much attention in BC development [ 62 ].…”

RETRACTED ARTICLE: Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation

“…Breast cancer is correlated with various extrinsic and intrinsic risk factors, such as environmental and genetic factor, tumor history in direct relatives, late menopause, early menarche and age more than 40 [2]. Reports have exhibited adipocyte secretome to contribute to and facilitate mammary tumor formation, which might provide new insights for the prevention of breast cancer [3]. Anthracyclines and trastuzumab are the extensively used drugs in breast cancer treatment protocol, which induce congestive heart failure as a side effect [4].…”