Aims
It has been well established that exercise is effective against tumour growth and spread of cancer. However, many cancer patients are unable to perform any strenuous physical activities due to the severity of the disease. Hence, we have voyaged to uncover the benefits of plasma extracellular vesicles (EVs) derived from mice and humans that were subjected to exercise on breast cancer progression.
Methods
Plasma EVs were isolated using size exclusion chromatography coupled with ultracentrifugation from mice subjected to high-intensity interval training (HIIT) exercise and sedentary mice. Effects of plasma EVs derived from exercise and sedentary mice on metastatic breast cancer were investigated using quantitative proteomic analysis, electron microscopy, western blotting, proliferation, migration assays, qPCR, orthotopic mouse models, IVIS imaging and immune cell profiling.
Results
When treated with plasma EVs of exercise mice (excEVs), a panel of breast cancer cells showed a significant reduction in proliferation and migration compared to PBS and sedentary mice (sedEVs). Importantly, orthotopic mouse models bearing metastatic breast cancer tumours showed a significant attenuation in tumour burden and metastasis in the presence of excEVs while modulating the immune cell profiling of the mice. Moreover, quantitative proteomic analysis of excEVs showed an upregulation of several tumour suppressor proteins. EVs overexpressing these molecules transferred anticancer properties to metastatic breast cancer cells confirming their role in attenuation of tumour growth and metastasis.
Conclusion
For the first time, we were able to show that plasma EVs derived from physically active mice could attenuate aggressive breast cancer tumour growth and metastasis.