According to the expression levels of LOX family members in HCC cells under different stiffness stimulation and the significance role of LOX family members in pre-metastatic niche [22, 25], we speculated that the secreted LOXL2 from HCC cells might mediate the linkage between higher matrix stiffness and pre-metastatic niche, and facilitate tumor distant metastasis. In addition, higher matrix stiffness stimulation significantly altered shape and spread area of HCC cells. This evidence concerns the gene LOXL2 and neoplasm.