Identification and funs tonal analysis of novel molecules that regulate tumor cell motility

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We have found that a tumor metastasis-related cell surface molecule CD44 can recognize not only hyaluronic acid (GlcA-GlcNAc) but also an essential moiety of chondroitin sulfate, GlcA/Ido-A-GaINAc. This indicates that CD44 can interact with various proteoglycans expressed by vascular endothelial cells as well as extracellular matrix (ECM) components. In addition, we found that hyaluronan (HA) degraded into oligosaccharides of a certain size range can induce proteolytic cleavage of CD44 from tumor cells and promote tumor cell motility. Furthermore, we found that tumor cells themselves produce hyaluronidases that can generate HA oligosaccharides, which in turn bind to tumor cell CD44 to promote CD44 cleavage and tumor motility. Other types of glycosaminoglycans also showed similar activities when they were degraded into oligomers. These results suggest that tumor cells and their ECMs can generate substances that promote tumor cell invasion. We have also made investigations on chemokines and chemokine binding molecules and found that chemokines can induce directional cell motility efficiently when they are immobilized on certain ECM components.