Document Detail


Alterations of cell surface carbohydrates and inhibition of metastatic property of murine melanomas by alpha 1,3 galactosyltransferase gene transfection.
MedLine Citation:
PMID:  7545089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three melanomas of C57BL/6 mice (BL6, JB/MS, and JB/RH) share several phenotypic properties. All these cells contain melanoma-specific ecotropic C-type retrovirus that encodes melanoma-associated antigen recognizable by MM2-9B6 mAb. They do not express H-2Kb molecules, and the alpha-galactosyl epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) they fail to react with soybean agglutinin (SBA), peanut agglutinin (PNA), and vicia villosa (VV) lectins. Previously, we found that failure of BL6 melanoma cells to express alpha-galactosyl epitopes is due to down-regulation of alpha 1,3 galactosyltransferase (alpha 1,3GT) gene expression. To evaluate the possible role of alpha-galactosyl cell membrane carbohydrates in regulation of metastatic properties, individual clones isolated from BL6, JB/MS, and JB/RH melanomas were transfected with alpha 1,3GT cDNA. This resulted in appearance of alpha-galactosyl epitopes, as well as of carbohydrates reacting with SBA, PNA, or VV lectins, but did not affect expression of H-2 class I molecules or melanoma-associated antigen. Appearance of SBA, PNA, and VV lectin binding carbohydrates in the alpha 1,3GT gene-transfected melanoma cells is a result of reduction of cell membrane sialylation and unmasking of these carbohydrates. Reduction in cell membrane sialylation in the alpha 1,3GT gene-transfected melanoma cells is probably due to the competition between alpha 1,3GT with alpha 2,3 sialyltransferase or alha 2,6 sialyltransferase for the common acceptor N-acetyllactosamine in the Golgi apparatus. As a result of this competition, cell membranes of alpha 1,3GT gene-transfected melanoma cells became galactosylated and less sialylated. In parallel with alteration of cell membrane carbohydrates, transfection of the alpha 1,3GT gene leads to the loss of metastatic properties of the transfected melanoma cells in the immunocompetent and immunosuppressed C57BL/6 mice. Thus, the use of specific glycosyltransferase cDNA transfection presents direct experimental confirmation of the importance of cell membrane carbohydrates in the regulation of metastatic properties of tumor cells.
Authors:
E Gorelik; L Duty; F Anaraki; U Galili
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  55     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-10-06     Completed Date:  1995-10-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4168-73     Citation Subset:  IM    
Affiliation:
Pittsburgh Cancer Institute, University of Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Carbohydrates / analysis*
Cell Membrane / chemistry
Epitopes*
Female
Galactosyltransferases / genetics*
Melanoma / chemistry,  secondary*
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Molecular Sequence Data
Transfection*
Trisaccharides / analysis*
Grant Support
ID/Acronym/Agency:
CA59903/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carbohydrates; 0/Epitopes; 0/Trisaccharides; 0/alpha-galactosyl epitope; EC 2.4.1.-/Galactosyltransferases; EC 2.4.1.87/beta-D-galactosyl-N-acetylglucosaminylglycopeptide alpha-1,3-galactosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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