Ramaiah Shashi K, Rittling Susan
Department of Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4467, USA.
Toxicol Sci. 2008 May;103(1):4-13. doi: 10.1093/toxsci/kfm246. Epub 2007 Sep 22.
Osteopontin (OPN) is a highly modified integrin-binding extracellular matrix glycophosphoprotein produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteoblasts, and tumor cells. Extensive research has elucidated the pivotal role of OPN in cell signaling that controls inflammation, tumor progression, and metastasis. OPN interaction with the integrin receptors expressed on inflammatory cells through its arginine-glycine-aspartate (RGD) and non-RGD motifs promote migration and adhesion of cells. In the liver, it has been reported that hepatic Kupffer cells secrete OPN facilitating macrophage infiltration into necrotic areas following carbon tetrachloride liver toxicity. Recent work has highlighted the role of OPN in inflammatory liver diseases such as alcoholic and nonalcoholic liver disease and T-cell-mediated hepatitis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interest, especially with regards to its role as a prognostic factor. OPN therefore appears to play an important role during liver inflammation and cancer. In this review we will present data to demonstrate the key role played by OPN in mediating hepatic inflammation (neutrophils, monocytes/macrophages, and lymphocytes) and its role in HCC. Greater understanding of the pathophysiologic role of OPN in hepatic inflammation and cancer may enable development of novel inflammation and cancer treatment strategies.
骨桥蛋白（OPN）是一种经过高度修饰的整合素结合细胞外基质糖磷蛋白，由免疫系统细胞、上皮组织、平滑肌细胞、成骨细胞和肿瘤细胞产生。广泛的研究已经阐明了OPN在控制炎症、肿瘤进展和转移的细胞信号传导中的关键作用。OPN通过其精氨酸 - 甘氨酸 - 天冬氨酸（RGD）和非RGD基序与炎症细胞上表达的整合素受体相互作用，促进细胞的迁移和黏附。在肝脏中，据报道肝库普弗细胞分泌OPN，促进巨噬细胞在四氯化碳肝毒性后浸润到坏死区域。最近的研究突出了OPN在酒精性和非酒精性肝病以及T细胞介导的肝炎等炎症性肝病中的作用。OPN在肝细胞癌（HCC）中的作用也引起了极大的关注，特别是其作为预后因素的作用。因此，OPN似乎在肝脏炎症和癌症过程中发挥重要作用。在本综述中，我们将展示数据以证明OPN在介导肝脏炎症（中性粒细胞、单核细胞/巨噬细胞和淋巴细胞）中所起的关键作用及其在HCC中的作用。对OPN在肝脏炎症和癌症中的病理生理作用有更深入的了解，可能有助于开发新的炎症和癌症治疗策略。
