Li Yu-Sheng, Deng Zhen-Han, Zeng Chao, Lei Guang-Hua
Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China,
Med Oncol. 2015 Jan;32(1):449. doi: 10.1007/s12032-014-0449-y. Epub 2014 Dec 17.
The primary bone malignancy osteosarcoma (OS) is a painful health burden, of which treatment remains a challenging problem. Identification of specific tumor biomarkers may help to investigate and develop the novel effective therapeutic approaches that have specific molecular target for the treatment of patients with OS. Osteopontin (OPN), a phosphorylated glycoprotein, is involved in many biological processes, such as biomineralization, bone remodeling and immune responses and has recently been reported to be associated with OS pathogenesis. Interestingly, both of the up- and down-regulation of OPN are involved in OS. During OS development, genetic or epigenetic disruption causes reduced expression of RUNX2 and OPN through the up-regulation of notch signaling pathway, leading to the development of OS. On the other hand, during hypoxic condition, upregulation of OPN induces the glucose uptake into hypoxic OS cells which is responsible for the OS cell proliferation and drug resistance. Recent evidences show that targeting OPN might be an important tool in OS therapeutics. This review has focused on the association of abnormal OPN expression with the pathogenesis of OS, the efficiency of OPN as a diagnostic tool for OS and the therapeutic aspects of OS by targeting OPN.
原发性骨恶性肿瘤骨肉瘤(OS)是一种令人痛苦的健康负担,其治疗仍然是一个具有挑战性的问题。识别特定的肿瘤生物标志物可能有助于研究和开发针对OS患者治疗的具有特定分子靶点的新型有效治疗方法。骨桥蛋白(OPN)是一种磷酸化糖蛋白,参与许多生物学过程,如生物矿化、骨重塑和免疫反应,最近有报道称其与OS发病机制有关。有趣的是,OPN的上调和下调都与OS有关。在OS发展过程中,遗传或表观遗传破坏通过上调Notch信号通路导致RUNX2和OPN表达降低,从而导致OS的发生。另一方面,在缺氧条件下,OPN的上调诱导缺氧OS细胞摄取葡萄糖,这与OS细胞增殖和耐药性有关。最近的证据表明,靶向OPN可能是OS治疗的重要工具。本综述重点关注OPN异常表达与OS发病机制的关联、OPN作为OS诊断工具的效率以及通过靶向OPN对OS进行治疗的方面。