Osteopontin up‐regulates metastatic potential of prostate cancer (PC3) cells through formation of CD44/MMP‐9 complex

The expression of osteopontin correlates with metastatic potential for several tumors. We generated stable prostate cancer cell (PC3) lines over expressing osteopontin (PC3/OPN), mutant osteopontin in its integrin £\v£]3 binding site (PC3/RGDƒ′RGA), and null for osteopontin (PC3/siRNA). OPN over expression increases the number of multinucleated giant cells and RANK‐L expression. An increase in CD44 surface expression, surface interaction of CD44/MMP‐9, MMP‐9 activity in the conditioned medium and cell migration was also observed in these cells, while a decrease in the above mentioned processes was observed in PC3/SiRNA and PC3/OPN(RGA) cells. A broad spectrum MMPs inhibitor GM6001 reduced cell migration. Although there is not much variation in the total cellular levels of CD44s or variant isoforms, an increase in the surface expression of three variant isoforms and CD44s was observed. This increase was not observed in PC3/OPN(RGA) cells. These results, taken together suggest some prognostic significance of OPN protein and integrin £\v£]3 signaling pathway in the possible vicious action of tumor cells and underlying pathology.