HYALURONAN - RHAMM MEDIATED CELL LOCOMOTION AND SIGNALING IN TUMORIGENESIS

Extracellular matrix molecules and their receptors are important regul ators of cell movement, adhesion and cytoskeletal organization. Adhesi on molecules can also serve to mediate signal transduction and can inf luence, and sometimes direct, the events required for tumorigenesis. T he extracellular matrix molecule, hyaluronan and its receptors have be en implicated in transformation and metastasis, in particular the proc esses of tumor cell motility and invasion. RHAMM (receptor for hyaluro nan mediated motility) is required for the cell locomotion of ras-tran sformed fibrosarcoma cells, cytokine stimulated fibrobasts and T lymph ocytes, malignant B cells, and breast carcinoma cells. HA:RHAMM intera ctions promote cell locomotion via a protein tyrosine kinase signal tr ansduction pathway that targets focal adhesions. The tyrosine kinase p p60(c-src) is associated with RHAMM in cells and is required for RHAMM mediated cell motility. It is possible that a RHAMM/src pathway induc es focal adhesions to signal the cytoskeletal changes required for ele vated cell motility seen in tumor progression, invasion and metastasis .