DIFFERENTIAL-EFFECTS OF SYNTHETIC SPHINGOSINE DERIVATIVES ON MELANOMACELL MOTILITY, GROWTH, ADHESION AND INVASION IN-VITRO

Cancer cell surface glycosphingolipids are considered to play a critic al role in tumor growth and metastasis, However, the implications of g lycoconjugates in the control of cell motility, which is considered to be involved in tumor invasion, are not fully understood, In this stud y, the effects of a series of synthetic sphingosine derivatives, obtai ned by the chemical transformation of azidosphingosines, on directiona l migration of K1735-M2 melanoma cells grown on type I collagen-coated surfaces were investigated, Following the application of 60 mu M (2R, 3S, 4E)-2,3-epimino-4-octadecen-3-ol (S4) the migration rate was 94+/ -10 mu m/day, compared with 377+/-22 mu m/day in the control experimen t. Six other analogues were not as potent, S4 also considerably down-m odulated melanoma single cell motility, Inhibition of motile activity was associated with changes in the actin filament organization as well as with changes in the number and distribution of vinculin plaques, M oreover, the compound reduced the attachment abilities of melanoma cel ls to basement membrane Matrigel, Tumor cell invasion, however, was le ss affected and proliferation remained unimpaired after treatment with S4, These data suggest at least one intracellular mode of action of t his particular synthetic sphingosine derivative by modulation of cytos keletal organization, Melanoma cell motility and growth may be control led independently via glycosphingolipids.