Recently, it has been reported that endothelial cell-derived exosomes mediate ECM crosslinking by upregulation of LOXL2 under hypoxic conditions [67], implying that it would be of interest to determine the noncancer source of LOXL4 carried by exosomes in tumor microenvironment and its role in regulating tumor metastasis through the herein demonstrated mechanisms in HCC. This evidence concerns the gene LOXL2 and hepatocellular carcinoma.