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

Abstract

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.

• Authors: H Yamamoto, A Oviedo, C Sweeley, T Saito, J R Moskal
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 18 Pg. 6822-9 (Sep 15 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11559557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin alpha3beta1
• Integrins
• Isoenzymes
• Polysaccharides
• Sialic Acids
• Sialyltransferases
• beta-Galactoside alpha-2,3-Sialyltransferase

Topics

• Animals
• Brain Neoplasms (genetics, metabolism, pathology)
• Extracellular Matrix (metabolism)
• Glioma (genetics, metabolism, pathology)
• Humans
• Integrin alpha3beta1
• Integrins (metabolism)
• Isoenzymes (genetics, metabolism)
• Polysaccharides (biosynthesis, metabolism)
• Rats
• Sialic Acids (metabolism)
• Sialyltransferases (genetics, metabolism)
• Transfection
• Tumor Cells, Cultured
• beta-Galactoside alpha-2,3-Sialyltransferase