Obesity and breast cancer: impact of vitamin D on the inflammatory adipose tumor microenvironment in obesity in a 3D co-culture model
2024
AOUN, Jessy | HABANJAR, Ola | NEHME, Rawan | Decombat, Caroline | DIAB-ASSAF, Mona | Caldefie-Chezet, Florence | Delort, Laetitia | Unité de Nutrition Humaine (UNH) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
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Показать больше [+] Меньше [-]Английский. Intorduction: Obesity is a recognized risk factor for breast cancer, the leading cause of cancer death worldwide. Vitamin D (vit D), a molecule with anti-inflammatory effects, is able to act on different cell types via the presence of its VDR receptor. Our aim was therefore to study the impact of vit D in a 3D culture model mimicking the breast tumor microenvironment of a person with obesity.METHODS: To this end, the effect of a physiological concentration of the active form of vit D was assessed in a 3D co-culture model between 3 cell types present in the microenvironment: M1 macrophages, cancer cells as tumoroids and pre-adipocytes (obtained from women with obesity) cultured as preadipospheroids or mature adipocytes as adipospheroids,RESULTS: The results show a decreased expression of adipocyte differentiation genes (leptin, adiponectin, HSL, aP2) in preadipospheroids, of inflammatory cytokines (IL-8, IL-6, TNFα, IL-1β, CXCL10) in pro-inflammatory M1 macrophages and of proliferation gene (PCNA) in tumoroids in the presence of preadipospheroids in the treated conditions compared to the non treated one. These results were not observed in the co-culture with adipospheroids. A decrease in IL-6 and an increase in IL-2 secretion in the supernatants were also observed with preadipospheroids.CONCLUSION: Vit D has therefore a more pronounced action on preadipospheroids, and could be used as a primary prevention for women with obesity at risk of breast canc
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