Effects of obesity on the dynamics of cancer cell invasion into adipose tissue

Tumor cell invasion into white adipose tissue (WAT) is an important step in the progression of breast cancer. While numerous studies have focused on the genetic influences on breast cancer, much less is known about the role of the mechanical properties of adipose tissue in tumor cell invasion. We have developed discrete element method (DEM) simulations of tumor cell invasion into WAT. We model the adipocytes as deformable particles that can explicitly change their shape in response to external forces and the cancer cells as active, sticky soft spheres. Prior experimental studies of breast cancer in mouse models have shown that the stiffness and size of the adipocytes increase when the mice have high-fat diets. Using DEM simulations, we show that the invasion depth of cancer cells into WAT decreases with increasing stiffness and size of the adipocytes. Experimental studies that induce breast cancer in mouse models show that tumor cells cause lipolysis in WAT and that rates of lipid loss are larger in mice with high-fat diets. In the DEM simulations, we show that rapid lipolysis can accelerate tumor cell invasion even in systems with stiff and densely packed adipocytes.