Research Projects

Breast cancer is the leading cause of cancer-associated mortality in women globally, with 90% of deaths due to metastasis. Newer treatment regimens are needed to combat metastasis. The tumor microenvironment plays a crucial role in the initiation and progression of breast cancer, with adipocytes driving tumor progression through mutual and dynamic crosstalk with tumor cell counterparts. Obesity is a high risk factor for breast cancer progression, metastasis, and drug resistance. Previous studies have shown the role of adipocyte-dependent signaling cascades in breast cancer metastasis, and obesity-mediated changes within the tumor microenvironment may promote metastasis. However, the underlying mechanisms involving highly orchestrated interaction between adipocytes and breast cancer cells permissive to metastasis in physiologically relevant environments are largely unexplored. Biophysical factors such as extracellular matrix density and orientation (topography) have been suggested as links between breast cancer metastasis and biophysical factors. A previous study demonstrated the role of substrate topography in promoting epithelial-to-mesenchymal transition, invasion, metastasis, and stemness in breast cancer cells. However, whether substrate topography influences adipocyte-breast cancer cell crosstalk leading to metastasis is still unknown. The aim is to investigate the contribution of matrix topography and cancer-associated adipocytes in modulating breast cancer metastasis using a 3-D in vitro model. Deciphering the heterotypic crosstalk as a function of substrate topography could provide new therapeutic targets against the tumor microenvironment and metastasis. The bioengineered 3-D metastatic model will also be used to screen potential therapeutic agents/metabolite inhibitors that can modulate ECM matrix alignment, making a non-permissive environment for metastasis, especially in obese patients.