Department of Orthopedic Surgery, Shanghai No. 6 People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Int J Oncol. 2013 Nov;43(5):1578-86. doi: 10.3892/ijo.2013.2067. Epub 2013 Aug 21.
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.
赖氨酰氧化酶（LOX）是一种细胞外基质（ECM）重塑酶，参与多种类型肿瘤的发生和发展。LOX 功能障碍可见于结直肠癌、乳腺癌和卵巢癌。然而，LOX 在骨肉瘤进展中的确切作用和分子机制尚不清楚。我们评估了 LOX 在人骨肉瘤细胞系和临床肿瘤样本中的作用，以确定该分子的功能。在我们的研究中，我们发现与正常组织样本相比，人骨肉瘤组织中 LOX mRNA 和蛋白的表达水平降低。此外，我们采用腺病毒介导的 LOX 在 U-2OS 和 HOS 细胞中的过表达来研究 LOX 在骨肉瘤细胞系中的作用。腺病毒介导的 LOX 过表达可有效增加骨肉瘤细胞系中 LOX 的表达水平，无论是在 mRNA 还是蛋白水平。LOX 表达增加抑制了人骨肉瘤细胞的增殖和迁移，并促进了其凋亡。此外，Ki-67 和 PCNA 的表达减少，MMP-2 和 MMP-9 的表达受到抑制。这些发现还表明，LOX 的作用可能是通过 PI3K/AKT 信号通路介导的，因为 LOX 介导的功能可以被 LOX 抑制剂β-氨基丙腈（β-APN）阻断。总之，我们的数据表明 LOX 可能是一种肿瘤抑制因子，可以被视为人类骨肉瘤的治疗靶点。
