Cancer cells transfer invasive properties through tracks, a novel collagen-associated extracellular vesicle entity

Abstract Metastasis is the leading cause of cancer-related deaths. During this process, tumor cells acquire invasive and migratory capacities in order to invade the surrounding tissues. To achieve this, the tumor microenvironment including the extracellular matrix (ECM) is altered to facilitate cancer cell proliferation and dissemination. Extracellular vesicles (EVs), such as exosomes or migrasomes, are already known to induce pro-tumor features such as migration, promoting tumor development and metastasis formation. Here we highlight a new type of EVs, referred as tracks, released by cancer cells during migration and specifically attached along collagen fibers. These tracks, identified by discoidin receptor 1 (DDR1) enrichment, are promoted when cell-ECM interactions are increased, such as in tumors. We characterized these tracks, their ultrastructure as well as their molecular composition in terms of proteins and nucleic acids, showing that they are different from classical EVs known so far. Moreover, these tracks are very stable structures and can be internalized by surrounding cells. After internalization, they modify the differentiation status and the phenotype of recipient cells, promoting epithelial to mesenchymal transition, matrix degradation and invasion. Thus, we identified a new class of collagen-associated EVs, tracks, that play a role in cell-cell communication by transferring invasive properties. Consequently, these cancer-related tracks could be a new player in the tumor invasion process.