Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues

Osteopontin has been implicated in the metastasis of tumors, and human tumo rs with high metastatic activity often express osteopontin at high levels, Osteopontin contains an arginine-glycine-aspartate (RGD) motif that is reco gnized by integrin family members to promote various cell activities includ ing attachment to substrate and it is abundant in bone, to which certain tu mors preferentially metastasize, Therefore, we investigated the role of ost eopontin in the experimental metastasis of tumor cells using recently estab lished osteopontin-deficient mice. B16 melanoma cells, which produce little osteopontin, were injected into the left ventricle of osteopontin-deficien t mice or wild-type mice. Animals were killed 2 weeks after injection. The number of tumors was reduced in the bones of osteopontin-deficient mice com pared with the bones in wild-type mice, The number of tumors in the adrenal gland also was reduced. To investigate the osteopontin effect on metastase s via a different route, we injected B16 melanoma cells into the femoral ve in. Through this route, the number of lung tumors formed was higher than in the intracardiac route and was again less in osteopontin-deficient mice co mpared with wild-type mice. In conclusion, in an experimental metastasis as say, the number of tumors found in bone (after intracardiac injection) and lung (after left femoral vein injection) was significantly reduced in osteo pontin-deficient mice compared with wild-type mice. Tumor numbers in other organs examined were small and not significantly different in the two situa tions.