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.

Lysyl Oxidase Is Predictive of Unfavorable Outcomes and Essential for Regulation of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma

“…It promotes cell growth and metastasis of a variety of cancer cells in vitro and in vivo [10,11,28,31,32], whereas other researchers found that LOX is a suppressor of proliferation and migration in human osteosarcoma cells [6]. In our study, the data from MTT assay demonstrated that siLOX intensively inhibited proliferative activity of MHCC-97-H and HepG2 cells.…”

“…and breast cancer [9][10][11], although evidence also points to LOX as a tumor suppressor [6], which indicates a dual role of LOX. Recent studies have shown that elevated expression of LOX propeptide, a LOX suppressor, inhibits the growth and migration of HCC cells [12], suggesting the involvement of LOX in HCC.…”

“…LOX belongs to the LOX family, which comprises five different enzymes (lysyl oxidase, lysyl oxidase-like 1, lysyl oxidase-like 2, lysyl oxidase-like 3, and lysyl oxidase-like 4), some being identified as oncogenes, tumor suppressors, and regulators of cell growth [4][5][6]. LOX plays a key role in many physiological processes, such as extracellular matrix stabilization and bone formation [7].…”

Lysyl oxidase mediates hypoxia-induced radioresistance in non-small cell lung cancer A549 cells

“…31 Other findings indicated that the effects of LOX may be mediated via the PI3K/AKT signaling pathway. 32 Kucharzewska et al reported that hypoxia/ LOX signaling activates PI3K/Akt pathway. 33 As PI3k/Akt pathway per se is oncogenic, activation of PI3k/Akt leads to DSB and genomic instability, 33,34 and it may also participate in angiogenesis, cell cycle arrest, and resistance to radiationinduced apoptosis.…”

Expressão gênica da família das lisil oxidases e papel funcional de LOX em astrocitomas

“…A maioria dos estudos de LOX foi realizada em tumores de mama, cabeça e pescoço, pulmão, colorretal, pâncreas, osteosarcoma e estômago Gao et al, 2010;Min et al, 2010;Lee et al, 2011;Sanchez et al, 2011;Bais et al, 2012;Eiseler et al, 2012;Xu et al, 2013;, Kim et al, 2014.…”