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Obesity has been linked with numerous health issues as well as an increased risk of breast cancer. Although effects of direct obesity in patient outcomes is widely studied, effects of exposure to obesity-related systemic influencesin uterohas been overlooked. In this study, we investigated the effect of multigenerational obesity on epithelial cell migration and invasion using decellularized breast tissues explanted from normal female mouse pups from a diet induced multigenerational obesity mouse model. We first studied the effect of multigenerational diet on the mechanical properties, adipocyte size, and collagen structure of these mouse breast tissues, and then, examined the migration and invasion behavior of normal (KTB-21) and cancerous (MDA-MB-231) human mammary epithelial cells on the decellularized matrices from each diet group. Breast tissues of mice whose dams had been fed with high-fat diet exhibited larger adipocytes and thicker and curvier collagen fibers, but only slightly elevated elastic modulus and inflammatory cytokine levels. MDA-MB-231 cancer cell motility and invasion were significantly greater on the decellularized matrices from mice whose dams were fed with high-fat diet. A similar trend was observed with normal KTB-21 cells. Our results showed that the collagen curvature was the dominating factor on this enhanced motility and stretching the matrices to equalize the collagen fiber linearity of the matrices ameliorated the observed increase in cell migration and invasion in the mice that were exposed to a high-fat diet. Previous studies indicated an increase in serum leptin concentration for those children born to an obese mother. We generated extracellular matrices using primary fibroblasts exposed to various concentrations of leptin. This produced curvier ECM and increased breast cancer cell motility for cells seeded on the decellularized ECM generated with increasing leptin concentration. Our study shows that exposure to obesityin uterois influential in determining the extracellular matrix structure, and that the resultant changes in collagen curvature is a critical factor in regulating the migration and invasion of breast cancer cells.

Breast cancer is one of the most common cancers in women, with the ability to metastasize to secondary organs, which is the main cause of cancer-related deaths. Understanding how breast tumors progress is essential for developing better treatment strategies against breast cancer. Until recently, it has been considered that breast cancer elicits a small immune response. However, it is now clear that breast tumor progression is either prevented by the action of antitumor immunity or exacerbated by proinflammatory cytokines released mainly by the immune cells. In this comprehensive review we first explain antitumor immunity, then continue with how the tumor suppresses and evades the immune response, and next, outline the role of inflammation in breast tumor initiation and progression. We finally review the current immunotherapeutic and immunoengineering strategies against breast cancer as a promising emerging approach for the discovery and design of immune system-based strategies for breast cancer treatment.