Document Detail

Differential effects of synthetic sphingosine derivatives on melanoma cell motility, growth, adhesion and invasion in vitro.
MedLine Citation:
PMID:  8970578     Owner:  NLM     Status:  MEDLINE    
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.
C Helige; J Smolle; R Fink-Puches; R Hofmann-Wellenhof; E Hartmann; T Bär; R R Schmidt; H A Tritthart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  14     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-01-09     Completed Date:  1997-01-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  477-89     Citation Subset:  IM    
Department of Medical Physics and Biophysics, University of Graz, Austria.
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MeSH Terms
Actins / ultrastructure
Cell Division / drug effects
Cell Movement / drug effects*
Chick Embryo
Dose-Response Relationship, Drug
Drug Combinations
Melanoma / metabolism,  secondary*,  ultrastructure
Neoplasm Invasiveness
Spheroids, Cellular / drug effects
Sphingosine / analogs & derivatives*,  chemistry
Reg. No./Substance:
0/Actins; 0/Drug Combinations; 0/Laminin; 0/Proteoglycans; 119978-18-6/matrigel; 123-78-4/Sphingosine; 9007-34-5/Collagen

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