In preliminary work, the investigator has identified a novel receptor-ligand interaction between the cytokine, osteopontin, and the homing receptor, CD44. Both receptor and ligand are typically expressed by activated lymphocytes, and may play important roles in lymphocyte homing. In addition, osteopontin and CD44 expression are associated with tumor cells, and may play important roles in the directed metastatic spread of specific tumor types. This project will investigate in detail the roles of variable RNA splicing and protein glycosylation in the functions of CD44 and osteopontin. The investigator will define post-receptor signaling events initiated by the binding of osteopontin to CD44, and will attempt to correlate these events with the cellular responses of apoptosis and migration. Transfection and antisense technologies will be used to define the contributions of the osteopontin-CD44 system to tumor growth and spread in vivo. These studies could provide important insights into the mechanism of tumor metastasis.
