Extracellular Vesicles from the Myocyte Secretome Contribute In Vitro to Creating an Unfavourable Environment for...

Area of Science:

• Cell Biology
• Oncology
• Biochemistry

Background:

• Cancer progression in skeletal muscle (SkM) is rare, with unclear underlying mechanisms.
• Extracellular vesicles (EVs) derived from SkM myocytes present a novel area for investigation.
• Understanding SkM-EVs' role in cancer is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To evaluate the anti-cancer potential of SkM (myocyte)-derived EVs (C2C12-EVs).
• To investigate the mechanisms by which C2C12-EVs affect cancer cell behavior and survival.
• To identify key molecular components within C2C12-EVs contributing to their anti-cancer activity.

Main Methods:

• Utilized murine in vitro models to assess C2C12-EVs' impact on lung carcinoma cells.
• Analyzed cancer cell colonization, apoptosis, proliferation, migration, and cell cycle.
• Performed proteomic analysis of C2C12-EV cargoes to identify functional pathways and enriched proteins.

Main Results:

• C2C12-EVs prevented lung carcinoma cell colonization of SkM cells.
• C2C12-EVs induced cancer cell apoptosis via lysosomal and mitochondrial pathways, activating caspases 3 and 9.
• C2C12-EVs inhibited cancer cell proliferation, induced S-phase arrest, and reduced migration. Proteomics revealed enrichment in pathways like HIF-1 and PI3K-Akt signaling.
• Decorin, a muscle-specific cytokine, was enriched in C2C12-EVs, potentially mediating anti-cancer effects.

Conclusions:

• SkM-derived C2C12-EVs exhibit significant anti-cancer properties, including apoptosis induction and inhibition of metastasis.
• C2C12-EVs modulate cancer cell functions through specific molecular cargo, such as decorin.
• These findings suggest C2C12-EVs hold promise as novel therapeutic agents against cancer metastasis.