The effect of lean or obese mouse adipocyte on the mesenchymal-to-epithelial transition of MDA-MB-231 cells in 3-dimensional culture

Asante, Emmanuel (2020) The effect of lean or obese mouse adipocyte on the mesenchymal-to-epithelial transition of MDA-MB-231 cells in 3-dimensional culture. Masters thesis, Memorial University of Newfoundland.

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Abstract

Obese breast cancer (BC) patients have at least 30% increased risk of death from BC compared to non-obese BC patients. This is because obesity is associated with larger tumor sizes and increased rates of metastasis. Obese BC patients respond poorly to treatment compared to non-obese patients, especially when diagnosed with the triple negative BC (TNBC) subtype. The reasons behind the poor treatment outcomes associated with obesity are not fully understood. The Christian Laboratory had previously established a novel 3-dimensional co-culture system that permitted the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, I demonstrated that lean and obese mice white adipose tissue could induce a mesenchymal-to-epithelial-transition (MET)-like effect in TNBC cells, thus furnishing the BC cells with properties that enable them to colonize and establish tumors in secondary organs. I have also shown that pro-MET factors are systemically secreted. Taken together this study suggests that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the MET-like effect induced adipose tissue could reduce metastasis.

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