Interaction between CD44 and osteopontin as a potential basis for metastasis formation.

Malignant growth has been associated with oncogene activation, telomerase activity, and expression of CD44 splice variants on the cell surface. Though dysregulation of growth control due to expression of oncogene products is fairly well understood, the mechanism of CD44-mediated homing and colony formation in specific tissues has remained cryptic. We have identified the cytokine osteopontin as a ligand for CD44. Osteopontin binds to naturally expressed and stably transfected CD44 in a manner that is specific, dose-dependent, inhibitable by anti-CD44 antibodies, insensitive to competition by Gly-Arg-Gly-Asp-Ser, and sensitive to competition by hyaluronate. The receptor-ligand interaction mediates chemotaxis or attachment, depending on presentation of osteopontin in soluble or immobilized form. In contrast, binding of CD44 to hyaluronate mediates aggregation or attachment but not chemotaxis. We found that two events occurring in malignancy-secretion of osteopontin and expression of CD44v-are linked in such a way that they may cause migration of tumor cells to specific sites of metastasis formation.