Radiation Effects on Breast Tissue-Derived Extracellular Matrix Hydrogels

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks estrogen receptor, progesterone receptor, and HER2, making it difficult to treat with conventional medicine. One common form of treatment involves surgery (lumpectomy or mastectomy) and chemotherapy followed by radiation therapy to eliminate residual tumor cells. About 20% of metastatic breast cancer patients have lymphopenia, which can be caused by radiation. It has recently been shown that radiation therapy can cause TNBC recurrence, and lymphopenic patients are especially vulnerable. The extracellular matrix (ECM) is an important part of breast tissue that provides structure for the tissue and supports cell growth. Breast tissue can experience radiation-induced fibrosis, which alters the ECM structure. Several components of the ECM have been identified as upregulated or downregulated in breast cancer. ECM hydrogels have been used to study physical tissue properties for use as a scaffolding biomaterial. An ECM hydrogel model was developed by digesting decellularized mammary fat pad tissue to evaluate how radiation modulates normal tissue response. ECM hydrogels were characterized for decellularization and changes in ECM components and structure. Culturing a murine TNBC cell line in ECM hydrogels demonstrated the potential for evaluating how radiation alters tumor cell invasion and proliferation, which could correlate to radiation-induced recurrence.