Breast cancer-released exosomes trigger cancer-associated cachexia to promote tumor progression

ABSTRACTEmerging evidence supports the pivotal roles of cancer-associated cachexia in biological behavior of breast cancer. However, the mediators and mechanisms that mediate cancer-induced cachexia remain unclear. Here, we show that breast cancer-derived exosomes alter adipocytes and muscle cells in terms of increased catabolism characterized by the release of metabolites. Likewise, tumor cells cocultivated with mature adipocytes or C2C12 exhibit an aggressive phenotype through inducing epithelial-mesenchymal transition. Mechanistically, we show that cancer cell-secreted miR-155 promotes beige/brown differentiation and remodel metabolism in resident adipocytes by downregulating the PPARγ expression, but does not significantly affect biological conversion in C2C12. In vitro the use of propranolol ameliorates tumor exosomes-associated cachectic wasting through upregulating the PPARγ expression. These results demonstrate that cancer-derived exosomes reprogram systemic energy metabolism and accelerate cancer...