Mouse Adipose Tissue Alters the Characteristic Morphology of Triple Negative Breast Cancer Cells In 3-Dimensional Culture

Breast cancer (BC) is the second leading cause of cancer related mortality amongst women globally. Obesity is one of the risk factors for BC. Obese BC patients have at least 30% increased risk of death from BC comparative to non-obese BC patients because obese women tend to have larger tumours and increased rates of metastasis. Moreover, obese BC patients respond poorly to treatment compared to non-obese patients, especially pre-menopausal women diagnosed with triple negative BC (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we have established a novel 3-dimensional (3D) co-culture system to co-culture adipocytes with TNBC cells in a manner that mimics an in vivo milieu as it includes the extracellular matrix. Using this system, we have shown that adipocytes secrete a factor(s) that induces a partial mesenchymal-to-epithelial-transition (MET) in TNBC cells; thus, furnishing the BC cells with properties that may promote secondary tumour formation. However, it is not known if lean or obese adipocytes affect TNBC differently. Here, we have found that adipocytes from lean and obese mice induce a partial MET in TNBC that differs depending on which adipose depot was analyzed. Ongoing work is focused on identifying this factor(s) and its expression in adipose tissue and in the circulation in obesity. Our findings may contribute to the development of future therapeutic targets for effective treatment of BC in lean and obese patients.