Alpha2,6-sialylation of cell-surface N-glycans inhibits glioma formation in vivo.

Authors: Yamamoto, H  Oviedo, A  Sweeley, C  Saito, T  Moskal, JR 
Citation: Yamamoto H, etal., Cancer Res. 2001 Sep 15;61(18):6822-9.
Pubmed: (View Article at PubMed) PMID:11559557

Human gliomas express very high levels of cell-surface alpha2,3-linked terminal sialic acids on glycoproteins bearing N-linked oligosaccharides, most notably on alpha3beta1 integrin, which is the predominant integrin found in these tumors. Alpha2,6-linked terminal sialic acids, however, are not expressed. Two stable transfectants were made using a tumorigenic human glioma cell line, U-373 MG. Galbeta1,4GlcNAc alpha2,6-sialyltransferase (ST6Gal I) transfectants were made to replace the endogenous alpha2,3-linked sialic acids with alpha2,6-linked sialic acids. And Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase (ST3Gal III) transfectants were made to increase further the expression of cell-surface, N-glycan, alpha2,3-linked sialic acids. Although ST3Gal III transfection resulted in increased invasivity when compared with parental U-373 MG and vector-transfected control cells in vitro, ST6Gal I transfection abolished invasion in vitro and induced alterations in both cell morphology, cell-spreading, and adhesion-mediated protein tyrosine phosphorylation. Furthermore, the ST6Gal I transfectants produced no intracranial tumors in severe combined immunodeficient mice, whereas parental U-373 MG cells, the vector-transfected control cells, and ST3Gal III-transfected U-373 MG cells did. These results suggest that both the linkage and expression levels of the terminal sialic acids of alpha3beta1 integrin N-glycans play an important role in glioma cell-extracellular matrix interactions. Thus, manipulating ST6Gal I gene expression may have therapeutic potential for the treatment of malignant gliomas.

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CRRD ID: 10043143
Created: 2015-05-14
Species: All species
Last Modified: 2015-05-14
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.