A new class of extracellular vesicles, Motile Vesicles (“MoVes”), carry whole genome DNA and are emitted during active cancer cell migration

Abstract Migrating cancer cells emit a diverse array of extracellular vesicles (EVs) that carry bioactive molecules, including DNA, which may mediate intercellular communication and metastatic progression. However, the mechanisms and biological significance of DNA packaging in EVs remain poorly understood. Here, we identify and characterize a novel class of large EVs (2–5 μm), termed Motile Vesicles (MoVes), which are selectively released during cancer cell migration and closely associated with epithelial–mesenchymal transition (EMT). Using scanning electron microscopy and live-cell imaging, we show that MoVes are actively shed by cancer cells—a phenomenon absent in normal epithelial cells. Whole-genome sequencing reveals that MoVes encapsulate the full genomic content of their parent cells, faithfully reflecting their mutational landscape. Proteomic profiling further distinguishes MoVes from other EV subtypes, with FAM3C—an interleukin-like EMT inducer—emerging as a specific molecular marker. These findings define MoVes as a cancer-specific EV population that carries genomic DNA during EMT and migration, unveiling new insights into extracellular DNA biology and potential mechanisms of cancer progression and metastatic dissemination.