Expression of lysyl oxidase in human osteosarcoma and its clinical significance: A tumor suppressive role of LOX in human osteosarcoma cells

Abstract

Lysyl oxidase (LOX) is an extracellular matrix (ECM) remodeling enzyme, which is involved in the development and progression of many types of tumors. LOX dysfunction is observed in colorectal, breast and ovarian cancer. However, the precise effects and molecular mechanisms of LOX action in osteosarcoma progression are still unknown. We evaluated the role of LOX in human osteosarcoma cell lines and clinical tumor samples in order to determine the function of this molecule. In our study, we showed that the expression level of LOX mRNA and protein were decreased in human osteosarcoma tissues as compared with normal tissue samples. In addition, we employed adenovirus-mediated overexpression of LOX in U-2OS and HOS cells to investigate the role of LOX in osteosarcoma cell lines. Adenovirus-mediated overexpression of LOX could efficiently increase the expression levels of LOX in osteosarcoma cell lines at both mRNA and protein levels. Increased expression of LOX inhibited the proliferation and migration of human osteosarcoma cells and promoted its apoptosis. Moreover, the Ki-67 and PCNA expression was decreased and MMP-2 and MMP-9 expression was inhibited. These findings also indicated that the effects of LOX may be mediated via the PI3K/AKT signaling pathway since LOX-mediated functions could be blocked by β-aminopropionitrile (β-APN), a LOX inhibitor. Taken together, our data indicated that LOX may be a tumor suppressor and could be regarded as a therapeutic target in human osteosarcoma.