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

Osteopontin has been implicated in the metastasis of tumors, and human tumors with high metastatic activity often express osteopontin at high levels. Osteopontin contains an arginine-glycine-aspartate (RGD) motif that is recognized by integrin family members to promote various cell activities including attachment to substrate and it is abundant in bone, to which certain tumors preferentially metastasize. Therefore, we investigated the role of osteopontin in the experimental metastasis of tumor cells using recently established osteopontin-deficient mice. B16 melanoma cells, which produce little osteopontin, were injected into the left ventricle of osteopontin-deficient 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 compared with the bones in wild-type mice. The number of tumors in the adrenal gland also was reduced. To investigate the osteopontin effect on metastases via a different route, we injected B16 melanoma cells into the femoral vein. Through this route, the number of lung tumors formed was higher than in the intracardiac route and was again less in osteopontin-deficient mice compared with wild-type mice. In conclusion, in an experimental metastasis assay, the number of tumors found in bone (after intracardiac injection) and lung (after left femoral vein injection) was significantly reduced in osteopontin-deficient mice compared with wild-type mice. Tumor numbers in other organs examined were small and not significantly different in the two situations.