Osteopontin-induced modifications of cellular functions.

Osteopontin (OPN) serves both a cell attachment function and a cell signalling function via the alpha v beta 3 integrin. We have investigated the action on mammalian cells of recombinant OPN made both in E. coli and in human cells. In its cell signalling capacity it initiates a signal transduction cascade that includes changes in the intracellular calcium ion levels and the tyrosine phosphorylation status of several proteins including pp60src and components of focal adhesion complexes. Effects on gene expression include suppression of the induction of nitric oxide synthase by inflammatory mediators. OPN can also reduce cell peroxide levels, promote the survival of cells exposed to hypoxia, and inhibit the killing of tumor cells by activated macrophages.