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In addition to being present within cells, we demonstrate a robust increase in the amount of TG2 and crosslinked fibronectin present within extracellular vesicle (EV) fractions derived from metastatic breast cancer cells. Confocal microscopy of these EVs suggests that FN undergoes fibrillogenesis on their surface via a TG2 and Tensin1-dependent process. Upon in vivo administration, the ability of tumor-derived EVs to induce metastatic niche formation and enhance subsequent pulmonary tumor growth requires the presence and activity of TG