The Effect of Ionising Radiation on the Properties of Tumour-Derived Exosomes and Their Ability to Modify the Biology of Non-Irradiated Breast Cancer Cells-An In Vitro Study.

Abstract

The vast majority of breast cancer patients require radiotherapy but some of them will develop local recurrences and potentially metastases in the future. Recent data show that exosomal cargo is essential in these processes. Thus, we investigated the influence of ionising radiation on exosome properties and their ability to modify the sensitivity and biology of non-irradiated cells. Exosomes were isolated from breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) irradiated with 2 Gy (Exo 2 Gy) or no irradiation (Exo 0 Gy). Despite some differences in their molecular profiles, they did not affect cell viability, proliferation, cell cycle phase distribution, and radioresistance; however, both populations showed the ability to modify cell migration and invasion potential, as confirmed by the downregulation of β-catenin, which is responsible for maintaining the epithelial phenotype. Interestingly, exosomes from irradiated BCa cells were more actively deposited in the endothelial cells (EA.hy926). Furthermore, exosomes tend to lower the expression of CD31, which is responsible for maintaining intact vascularity. This preliminary study demonstrates the vital role of exosomes and their altered profile due to irradiation in the pathobiology of breast cancer.