SPHINGOSINE-1-PHOSPHATE INHIBITS EXTRACELLULAR-MATRIX PROTEIN-INDUCEDHAPTOTACTIC MOTILITY BUT NOT ADHESION OF B16 MOUSE MELANOMA-CELLS

Sphingosine-1-phosphate (Sph-1-P), the initial product of Sph cataboli sm, inhibited chemotactic motility of a few lines of tumor cells [(199 2) Proc. Natl. Acad. Sci. USA 89, 9686]. We now report that Sph-1-P ev en at very low concentration (10-100 nM) inhibits integrin-dependent m otility of melanoma cells induced by extracellular matrix (ECM), altho ugh it did not affect integrin-dependent adhesion to ECM. Other Sph-re lated compounds tested (including sphinganine-1-P) were much less effe ctive than Sph-1-P at inhibiting motility, and also had no effect on i ntegrin-dependent adhesion of tumor cells to ECM. Our findings suggest that Sph-1-P inhibits actin filament reorganization by affecting cyto plasmic connection to integrin in ECM-stimulated motility of melanoma cells.