Differential effects of synthetic sphingosine derivatives on melanoma cell motility, growth, adhesion and invasion in vitro.
Cancer cell surface glycosphingolipids are considered to play a critical role in tumor growth and metastasis. However, the implications of glycoconjugates in the control of cell motility, which is considered to be involved in tumor invasion, are not fully understood. In this study, the effects of a series of synthetic sphingosine derivatives, obtained by the chemical transformation of azidosphingosines, on directional migration of K1735-M2 melanoma cells grown on type I collagen-coated surfaces were investigated. Following the application of 60 microM (2R, 3S, 4E)-2, 3-epimino-4-octadecen-3-ol (S4) the migration rate was 94 +/- 10 microns/day, compared with 377 +/- 22 microns/day in the control experiment. Six other analogues were not as potent. S4 also considerably down-modulated 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. Moreover, the compound reduced the attachment abilities of melanoma cells to basement membrane Matrigel. Tumor cell invasion, however, was less affected and proliferation remained unimpaired after treatment with S4. These data suggest at least one intracellular mode of action of this particular synthetic sphingosine derivative by modulation of cytoskeletal organization. Melanoma cell motility and growth may be controlled independently via glycosphingolipids.
Helige
C
C
Department of Medical Physics and Biophysics, University of Graz, Austria.
Smolle
J
J
Fink-Puches
R
R
Hofmann-Wellenhof
R
R
Hartmann
E
E
Bär
T
T
Schmidt
R R
RR
Tritthart
H A
HA
D000199:Actins / Q000648:ultrastructure; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002642:Chick Embryo; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007797:Laminin; D008545:Melanoma / Q000378:metabolism / Q000556:secondary* / Q000648:ultrastructure; D051379:Mice; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D018874:Spheroids, Cellular / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry
D000199:Actins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D013110:Sphingosine