Motile vesicles (MoVes) are a cancer cell migration-associated extracellular vesicle population

Migrating cancer cells release diverse extracellular vesicles (EVs) that carry cargo capable of influencing tumour progression and intercellular communication. However, the mechanisms by which intracellular components are incorporated into EVs remain poorly understood. Here we identify and characterize a previously undescribed population of large EVs (2-5 μm), termed motile vesicles (MoVes), that are generated during active cancer cell migration and associated with epithelial-mesenchymal transition. Comparative analyses across EV populations show that MoVes display distinct ultrastructural features, molecular composition and sedimentation behaviour. Live-cell imaging and scanning electron microscopy reveal that MoVes arise from trailing-edge retraction during mesenchymal migration and are actively shed by cancer cells but rarely by non-transformed cells. MoVes contain genomic DNA spanning the genome of the parent cell, recapitulating its mutational landscape, as well as organelles and proteins associated with epithelial-mesenchymal transition. Moreover, MoVes-associated mitochondrial cargo can enhance oxidative phosphorylation in recipient cells. Together, these findings identify MoVes as a cancer cell migration-associated EV population capable of disseminating genomic DNA and organelles.