摘要Carcinoma-associated fibroblasts(CAFs)are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix(ECM).The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase(LOX).Small extracellular vesicles(sEVs)mediate cell-cell communication.However,the interactions between sEVs and the ECM remain unclear.Here,we demonstrated that sEVs released from oral squamous cell carcinoma(OSCC)-derived CAFs induce collagen crosslinking,thereby promoting epithelial-mesenchymal transition(EMT).CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking,and a LOX inhibitor or blocking antibody suppressed this effect.Active LOX(αLOX),but not the LOX precursor,was enriched in CAF sEVs and interacted with periostin,fibronectin,and bone morphogenetic protein-1 on the surface of sEVs.CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I,and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I.CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway.Taken together,these findings reveal a novel role of CAF sEVs in tumor ECM remodeling,suggesting a critical mechanism for CAF-induced EMT of cancer cells.