THE ROLE OF EXERCISE TRAINING AND SKELETAL MUSCLE-DERIVED EXOSOMES ON THE PRE-METASTATIC NICHE FORMATION

Abstract

Pre-metastatic niche is the result of the combined systemic effects of tumor-secreted factors and tumor-shed extracellular vesicles (e.g. exosomes) that promote temporal sequence of events during the evolution of pre-metastatic niche. Aerobic exercise training reduces the incidence of several types of cancer and attenuates tumor growth in different cancer models. However, the effects of exercise training on the pre-metastatic niche are completely unknown. Here, we plan to investigate the functional and molecular mechanism of exercise training on the pre-metastatic niche formation. For a better characterization of exercise training, we will determine the role of acute and chronic aerobic exercise training on mobilization and uptake of tumor-derived exosome by cells at distant sites. Moreover, we will verify the ability of skeletal muscle-derived exosomes to compete with cancer-derived exosomes for being uptaken by cells at distant sites. Finally, we will investigate the effects of exercise training skeletal muscle-derived exosomes on bone marrow education by tumor-derived exosomes.