Invited Talk

Biophysical Contributions of Adipose Tissue to Breast Cancer Invasion

Garrett Beeghly, Adrian Shimpi

Cornell University, Department of Biomedical Engineering, 157 Weill Hall Ithaca, NY 14853, USA

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Mammary adipose tissue is an essential component of the breast cancer microenvironment and regulates local invasion of tumor cells during the metastatic cascade. Here, we focus on how physical properties of adipocytes and the surrounding extracellular matrix (ECM) regulate disease progression. Coupling histology, mechanical characterization, and discrete element method (DEM)-based mathematical modeling, we find that inherent heterogeneity of adipocyte size, stiffness, and packing fraction influence the mode and extent of tumor invasion. To isolate specific contributions from the ECM, we use a cell-derived matrix (CDM) model deposited by stromal cells isolated from murine mammary adipose tissue. Breast cancer cells cultured on CDMs exhibit elongated morphology and increased phosphorylation of proteins associated with cytoskeletal remodeling and migration relative to conventional tissue culture plastic. Furthermore, these cells increase hyaluronic acid production which is associated with an invasive, stem-like phenotype and transcriptomic changes predictive of worse patient survival. Together our results highlight how biophysical characteristics of adipose tissue contribute to breast cancer invasion.