1. Contribution of adipose stem cells from obese subjects to hepato-or breast-carcinoma tumorogenesis, through promotion of Th17 cells
- Author
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CHEHIMI, Marwa, Delort, Laetitia, Vidal, Hubert, Caldefie-Chezet, Florence, Eljaafari, Assia, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Cancéropôle Lyon Auvergne Rhône-Alpes (CLARA). FRA., ProdInra, Archive Ouverte, Hospices Civils de Lyon (HCL), Centre de Recherche en Nutrition Humaine (CRNH). FRA., Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université
- Subjects
obesity ,culture cellulaire ,Th17 lymphocytes ,cellule humaine ,hepatic cancer ,cancer du sein ,[SDV]Life Sciences [q-bio] ,obese adipose stem cells ,tissu adipeux ,breast cancer ,mammary malignant tumor ,adipose tissue ,[SDV] Life Sciences [q-bio] ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,obésité ,inflammation ,Alimentation et Nutrition ,Food and Nutrition ,cancer ,microbial culture ,cancer du foie ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,patient obèse - Abstract
SESSION 4 - BREAST CANCER: FROM EXPERIMENTAL APPROACH TO CLINICAL; IntroductionAs 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) werecollected from blood donors. PHA-activated co-cultures of obASC/MNC, which increase secretion of IL-17A, IL-1b and 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 qRTPCR. Expression of CXCR4 was measured by flow cytometry. Results: CM from 48 hr PHA-activated-ASC/MNC co-cultures enhanced IL-1b, VEGFa, IL-8 TNFa and 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-1b, IL-6, IL-8 and VEGF-a mRNA expression 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 tumors
- Published
- 2017