INTERACTION BETWEEN CD44 AND OSTEOPONTIN AS A POTENTIAL BASIS FOR METASTASIS FORMATION

Malignant growth has been associated with oncogene activation, telomer ase activity, and expression of CD44 splice variants on the cell surfa ce. Though dysregulation of growth control due to expression of oncoge ne 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. Oste opontin binds to naturally expressed and stably transfected CD44 in a manner that is specific, dose-dependent, inhibitable by anti-CD44 anti bodies, insensitive to competition by Gly-Arg-Gly-Asp-Ser, and sensiti ve to competition by hyaluronate. The receptor-ligand interaction medi ates chemotaxis or attachment, depending on presentation of osteoponti n in soluble or immobilized form. In contrast, binding of CD44 to hyal uronate mediates aggregation or attachment but not chemotaxis. We foun d that two events occurring in malignancy-secretion of osteopontin and expression of CD44v-are linked in such a way that they may cause migr ation of tumor cells to specific sites of metastasis formation.