Sphingosine-1-phosphate inhibits extracellular matrix protein-induced haptotactic motility but not adhesion of B16 mouse melanoma cells.

Sphingosine-1-phosphate (Sph-1-P), the initial product of Sph catabolism, inhibited chemotactic motility of a few lines of tumor cells [(1992) Proc. Natl. Acad. Sci. USA 89, 9686]. We now report that Sph-1-P even at very low concentration (10-100 nM) inhibits integrin-dependent motility of melanoma cells induced by extracellular matrix (ECM), although it did not affect integrin-dependent adhesion to ECM. Other Sph-related compounds tested (including sphinganine-1-P) were much less effective than Sph-1-P at inhibiting motility, and also had no effect on integrin-dependent adhesion of tumor cells to ECM. Our findings suggest that Sph-1-P inhibits actin filament reorganization by affecting cytoplasmic connection integrin in ECM-stimulated motility of melanoma cells.