Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
Curr Mol Med. 2010 Feb;10(1):71-81. doi: 10.2174/156652410791065381.
Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; this is also reflected by increased levels of OPN in the circulation. Thus, increased OPN levels the plasma are an effect of tumor growth and progression. Functionally, high OPN levels are determinative of higher incidence of bone metastases in mouse models and are clinically correlated with metastatic bone disease and bone resorption in advanced breast cancer patients. Several research efforts have been made to therapeutically target and inhibit the activities of OPN. In this article we have reviewed OPN in its role as an effector of critical steps in tumor progression and metastasis, with a particular emphasis on its role in facilitating bone metastasis of breast cancer. We have also addressed the role of the host-derived OPN in influencing the malignant behavior of the tumor cells.
骨桥蛋白(OPN)是一种基质细胞蛋白,在人体的多种组织中产生,在骨骼中含量最丰富。它也由癌细胞产生,并在癌症的生长、进展和转移中起决定性作用。临床上,已经报道 OPN 在肿瘤细胞本身中上调;这也反映在循环中 OPN 水平的增加。因此,血浆中 OPN 水平的升高是肿瘤生长和进展的结果。从功能上讲,高水平的 OPN 决定了小鼠模型中骨转移的发生率更高,并且与晚期乳腺癌患者的转移性骨疾病和骨吸收具有临床相关性。已经进行了一些研究工作来治疗性地靶向和抑制 OPN 的活性。在本文中,我们回顾了 OPN 在肿瘤进展和转移的关键步骤中的作用,特别强调了它在促进乳腺癌骨转移中的作用。我们还讨论了宿主来源的 OPN 在影响肿瘤细胞恶性行为中的作用。