Role of osteopontin in cellular signaling and toxicant injury

Osteopontin (OPN) is a glycosylated phosphoprotein found in all body fluids and in the proteinaceous matrix of mineralized tissues. It can function bo th as a cell attachment protein and as a cytokine, delivering signals to ce lls via a number of receptors including several integrins and CD44. Express ion of OPN is enhanced by a variety of toxicants, especially those that act ivate protein kinase C. In its capacity as a signaling molecule, OPN can mo dify gene expression and promote the migration of monocytes/macrophages up an OPN gradient. It has both inflammatory and anti-inflammatory actions. So me experiments suggest that it may inhibit apoptosis, possibly contributing to the survival of cells in response to toxicant injury. Elevated OPN expr ession often correlates with malignancy and has been shown to enhance the t umorigenic and/or metastatic phenotype of the cancer cell. Recent studies h ave revealed that OPN plays critical roles in bone remodeling and cell-medi ated immunity.