Mechanical Properties of Adipose Tissue Mediate Breast Cancer Invasion

Metastasis is the leading cause of death in patients with advanced breast cancer and increases in frequency with obesity. An increased invasion depth of cancer cells into adipose tissue is also strongly correlated with breast cancer metastasis. Experimental measurements in mouse models reveal that the stiffness of adipocytes increases with obesity. This observation raises the following question: how can breast cancer invade more rapidly into adipose tissue when adipocytes are stiffer? To address this question, we carried out discrete element method simulations of breast cancer invasion into adipose tissue in three dimensions, where cancer cells are modeled as active, adhesive spheres and adipocytes are modeled as deformable polyhedra. We find that increasing the adipocyte stiffness strongly suppresses breast cancer invasion. Thus, variations in adipocyte stiffness can give rise to regions of the adipose tissue that are more susceptible to tumor invasion than others. In addition, we show that tumor-induced lipid loss (lipolysis) promotes cancer cell invasion. These results suggest that lipolysis plays a crucial role in enhancing cancer invasion, especially in the case of high-fat diets. These findings provide potential therapeutic target to mitigate breast cancer metastasis.