Effects of exercise-induced extracellular vesicles on triple negative breast cancer cells

Abstract

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that is extremely difficult to treat due to the lack of progesterone, estrogen, and Her2 receptors in and/or on the cell. Currently, indicated treatment methods include surgery, radiation therapy, and chemotherapy, which are invasive and generally have negative side effects on the patient. This creates the need for a less invasive and more effective treatment method. Ongoing research shows that exercise can decrease TNBC tumor growth, suggesting that physical activity releases a systemic mediator of cancer growth into the bloodstream. It is hypothesized that these mediators are released via a type of extracellular vesicle. Extracellular vesicles (EVs) can carry miRNAs that cause repression of protein translation, perhaps resulting in downstream effects relevant to cancer survival, proliferation, and invasiveness. These miRNAs could be identified and potentially used to target and treat TNBC tumors. In this study, healthy male participants completed acute resistance exercise training and had blood taken before and after exercise, which was used to isolate EVs. We gathered preliminary data suggesting that EV treatment reduces the proliferation of a TNBC cell line, but not of an epithelial mammary cell line. Additionally, using phospho-arrays, we observed a decrease in activation status of several signaling proteins in EV treated TNBC cells, which may be contributing to the changes in proliferation. The goal of this study was to determine the effects of exercise induced EVs on proliferation, phosphorylation of kinases, as well as markers of differentiation and apoptosis to better understand the molecular mechanisms through which exercise slows tumor growth in TNBC.