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Breast cancer is the most common cancer in women worldwide.The breast consists of a mammary gland organised into ducts and lobules and surrounded by a stromal fraction, mostly composed of adipose tissue. Breast tumours derive from epithelial cells of the mammary gland, and develop in a stroma, rich in adipose tissue, with which there is dynamic and reciprocal communication via secreted factors.Many risk factors increase the incidence of breast cancer. Using breast adipocytes from human samples, differentiated in vitro, we show in this work that obesity, menopausal status, and breast density have no local effect in the dialogue between breast adipocytes and breast tumour cells. We also show that mammary adipocytes release fatty acids which can be captured by mammary tumour cells, via the CD36 transporter, stimulating their growth and invasion. Our work also shows that the expression of CD36 is sufficient to induce these effects, and to activate the fatty acid oxidation pathway in vitro. Understanding the mechanisms induced by CD36 on the aggressiveness of tumour cells will allow us to consider this protein as a biomarker or a therapeutic target in breast cancer., Le cancer du sein est le cancer le plus fréquent chez la femme dans le monde. Le sein se compose d’une glande mammaire organisée en canaux et lobules et entourée d’une fraction stromale, majoritairement composée de tissu adipeux. Les tumeurs mammaires dérivent des cellules épithéliales de la glande mammaire, et se développent dans un stroma riche en tissu adipeux, avec lequel il existe une communication dynamique et réciproque via des facteurs secrétés. De nombreux facteurs de risque augmentent l’incidence des cancers du sein. En utilisant des adipocytes mammaires issus de prélèvement humains, différenciés in vitro, nous montrons dans ces travaux que l’obésité, le statut ménopausique, et la densité mammaire, n’ont pas d’effet local dans le dialogue entre adipocytes mammaires et cellules tumorales mammaires. Nous montrons également que les adipocytes mammaires libèrent des acides gras qui peuvent être captés par les cellules tumorales mammaires, via le transporteur CD36, stimulant leur croissance et leur invasion. Nos travaux montrent aussi que l’expression de CD36 suffit à induire ces effets, et à activer la voie d’oxydation des acides gras in vitro. La compréhension des mécanismes qu’induit CD36 sur l’agressivité des cellules tumorales permettra d’envisager cette protéine comme un biomarqueur ou une cible thérapeutique dans les cancers du sein.

International audience; Breast adiposity is correlated with body mass index, menopausal status and mammary density. We here wish to establish how these factors influence the cross-talk between breast adipocytes and normal or malignant breast cells. Adipocyte-derived stem cells (ASCs) were obtained from healthy women and classified into six distinct groups based on body mass index, menopausal status and mammary density. The ASCs were induced to differentiate, and the influence of their conditioned media (ACM) was determined. Unexpectedly, there were no detectable differences in adipogenic differentiation and secretion between the six ASC groups, while their corresponding ACMs had no detectable influence on normal breast cells. In clear contrast, all ACMs profoundly influenced the proliferation, migration and invasiveness of malignant breast cells and increased the number of lipid droplets in their cytoplasm via increased expression of the fatty acid receptor CD36, thereby increasing fatty acid uptake. Importantly, inhibition of CD36 reduced lipid droplet accumulation and attenuated the migration and invasion of the breast cancer cells. These findings suggest that breast-associated adipocytes potentiate the invasiveness of breast cancer cells which, at least in part, is mediated by metabolic reprogramming via CD36-mediated fatty acid uptake.