Contribution of adipose stem cells from obese subjects to hepato-or breast-carcinoma tumorogenesis, through promotion of Th17 cells

Introduction:As opposed with lean adipose tissues (AT), obese AT are heavily infiltrated with variety of inflammatory cells. Among them, Th17 cells are found not only within AT, but also in the periphery in obese subjects. We have demonstrated that AT-derived stem cells (ASC), or their progenitors, contribute to inflammation through promotion of Th-17 cells, provided that they are issued from obese-, but not lean-AT (Diabetes, 2015; Adipocyte, 2016). Because obesity is associated with increased prevalence of various cancers, including hepatic or breast cancer, we postulated herein that ASC-mediated promotion of Th17 cells might result in tumorogenesis progression.Materials and Methods:Human ASC were isolated from WAT of obese donors (obASC). Mononuclear cells (MNC) were collected from blood donors. PHA-activated co-cultures of obASC/MNC, which increase secretion of IL-17A, IL--6, were performed. Conditioned media (CM) were collected from such cultures, and added to HuH7 (hepato-carcinoma cell line) or MCF-7 / MDA-MB-231 (breast carcinoma cell line) cultures for 24h. mRNA profiles were measured by qRT-PCR. Expression of CXCR4 was measured by flow cytometry.Results:CM from 48 hr PHA-activated-ASC/MNC co-cultures enhanced IL--8 TNF-IL-6 mRNA expression in HUH7 by almost 700, 2, 3, 3, and 6-fold, respectively. A putative effect of CM on HUH7 invasiveness was supported by 2a –fold, and 3-fold increase in MMP9, and CXCR4 expression, respectively. In addition, CM also increased IL--6, IL-8 and VEGF-in both MCF-7 and MDA-MB-231 cell lines.Conclusion:Our results suggest that the interaction of ob ASC with immune cells contribute to an inflammatory environment, able to impact hepato- or breast-carcinoma cell secretion profile, and/or invasiveness, either through propagation of inflammatory cytokines outside adipose tissues, or ASC migration inside tumor