Osteopontin (OPN) serves both a cell attachment function and a cell signalling function via the alpha v beta 3 integrin. In its cell attachment capacity it can promote attachment of both osteoclasts to bone hydroxyapatite and various other cell types to basement membrane/extracellular matrix. 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 paxillin. Effects on gene expression include suppression of the induction of nitric oxide synthase by inflammatory mediators. OPN can also reduce cell oxidant levels and inhibit the killing of tumor cells by activated macrophages and endothelial cells. We hypothesize that those cancer cells that produce OPN at elevated levels can suppress the oxidative burst, inhibit NO production, and thus protect themselves from killing by specific host cell types.