Pathophysiological Role of Osteopontin in Hepatic Inflammation, Toxicity, and Cancer

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.