Oncogenic effects of ECM remodeling in obesity and breast cancer
Mackenzie L. Hawes, M. D. Moody, Caroline H. Rinderle, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin
Abstract
Extracellular matrix (ECM) components are key regulators in breast cancer progression, as ECM remodeling is essential for breast cancer cells to invade into surrounding tissue. This process is characterized by the alignment of fibrillar collagens, breakdown of basement membrane components, and increased interstitial collagen stiffness. In patients with obesity, pre-existing ECM changes, including excessive collagen deposition and heightened matrix stiffness, mimic alterations detected in breast cancer. Given that obesity is a predictor of poor prognosis and resistance to treatment in breast cancer, it is crucial to understand how ECM conditioned by obesity affects disease outcomes. In this review, we highlight known ECM changes that occur with breast cancer and obesity and describe how these changes impact cancer cell metastasis, disease progression, and the breast cancer tumor microenvironment. We examine how obesity driven ECM remodeling affects treatment response and resistance. Further, we discuss how the compounding factor of age contributes to remodeling and current preclinical models of ECM in breast cancer.