α2, 6-sialylation of cell-surface N-glycans inhibits glioma formation in vivo

Hirotaka Yamamoto, Angelica Oviedo, Charla Sweeley, Tasuku Saito, Joseph R. Moskal

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Human gliomas express very high levels of cell-surface α2, 3-linked terminal sialic acids on glycoproteins bearing N-linked oligosaccharides, most notably on α3β1 integrin, which is the predominant integrin found in these tumors, α2, 6-linked terminal sialic acids, however, are not expressed. Two stable transfectants were made using a tumorigenic human glioma cell line, U-373 MG. Galβ1, 4GlcNAc α2, 6-sialyltransferase (ST6Gal I) transfectants were made to replace the endogenous α2, 3-linked sialic acids with α2, 6-linked sialic acids. And Galβ1, 3(4)GlcNAc α2, 3-sialyltransferase (ST3Gal III) transfectants were made to increase further the expression of cell-surface, N-glycan, α2, 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 α3β1 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.

Original languageEnglish (US)
Pages (from-to)6822-6829
Number of pages8
JournalCancer Research
Volume61
Issue number18
StatePublished - Sep 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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