Johnston Nicholas I F, Gunasekharan Vignesh Kumar, Ravindranath Amod, O'Connell Ciara, Johnston Patrick G, El-Tanani Mohamed K
Centre for Cancer Research and Cell Biology, Queen's University, Belfast, United Kingdom.
Front Biosci. 2008 May 1;13:4361-72. doi: 10.2741/3009.
Osteopontin (OPN) is a glycophosphoprotein cytokine that has multiple functions. OPN is expressed and secreted by various cells, and has a role in cell adhesion, chemotaxis, prevention of apoptosis, invasion, migration and anchorage-independent growth of tumor cells. Extensive research has demonstrated the pivotal participation of OPN in the regulation of cell signaling which controls neoplastic and malignant transformation. The elevated expression of OPN has been observed in a variety of cancers. OPN has been linked with tumor metastasis and signifies a poor prognosis for the patient. This review details the mechanisms by which OPN facilitates these pathological events. It will also show that gaining an understanding of the mechanism of OPN's action at a cellular level has led to the development of a number of therapeutic strategies against the cytokine. These include inhibiting its expression, antagonizing cell surface receptor activation and blocking downstream cell signaling pathways. In addition to the potential of these therapies, serum levels of OPN could be used as a diagnostic and prognostic marker. The authors propose that with further research and development, osteopontin directed treatment could greatly enhance outcomes for cancer patients.
骨桥蛋白(OPN)是一种具有多种功能的糖磷蛋白细胞因子。OPN由多种细胞表达和分泌,在细胞黏附、趋化性、防止细胞凋亡、肿瘤细胞侵袭、迁移和非锚定依赖性生长中发挥作用。广泛的研究表明,OPN在调控控制肿瘤形成和恶性转化的细胞信号传导中起着关键作用。在多种癌症中都观察到OPN表达升高。OPN与肿瘤转移有关,意味着患者预后不良。本综述详细阐述了OPN促进这些病理事件的机制。还将表明,在细胞水平上对OPN作用机制的了解已促成了多种针对该细胞因子的治疗策略的发展。这些策略包括抑制其表达、拮抗细胞表面受体激活以及阻断下游细胞信号通路。除了这些治疗方法的潜力外,OPN的血清水平可作为诊断和预后标志物。作者提出,随着进一步的研究和开发,针对骨桥蛋白的治疗可大大改善癌症患者的治疗效果。