Cancer Cell-Derived Small Extracellular Vesicles Are Associated with Impaired C2C12 Myoblast Differentiation

Cancer cachexia is a complex metabolic syndrome characterized by progressive skeletal muscle wasting and poor clinical outcomes. Previous studies have mainly focused on the association between cancer-derived extracellular vesicles and atrophy of differentiated myotubes, whereas their effects on myoblast differentiation markers have not been sufficiently elucidated. In this exploratory in vitro study, vesicle fractions isolated from MC38, CT26, MCA205, and B16F10 cancer cell lines under serum-deprived conditions were referred to as small extracellular vesicles (sEVs) and used to treat C2C12 myoblasts during differentiation. Compared with the control group, the sEV-treated groups showed reduced myotube diameter and differentiation area on day 6, while the mRNA expression patterns of MyoD, MyoG (Myogenin), MRF4, Myf5, Pax7, and several MHC isoforms showed time-dependent changes. GO/KEGG analysis of commonly identified proteins revealed enrichment of terms related to mRNA metabolism, the cell cycle, and the proteasome. These findings suggest that treatment with cancer cell-derived sEVs may be associated with impaired in vitro differentiation of C2C12 myoblasts.