Overexpression of ST6GalNAcV, a ganglioside-specific α2,6- sialyltransferase, inhibits glioma growth in vivo

Roger A. Kroes, Huan He, Mark Emmett, Carol L. Nilsson, Franklin E. Leach, I. Jonathan Amster, Alan G. Marshall, Joseph R. Moskal

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Aberrant cell-surface glycosylation patterns are present on virtually all tumors and have been linked to tumor progression, metastasis, and invasivity. We have shown that expressing a normally quiescent, glycoprotein-specific α2,6-sialyltransferase (ST6Gal1) gene in gliomas inhibited invasivity in vitro and tumor formation in vivo. To identify other glycogene targets with therapeutic potential,we created a focused 45-mer oligonucleotide microarray platform representing all of the cloned human glycotranscriptome and examined the glycogene expression profiles of 10 normal human brain specimens, 10 malignant gliomas, and 7 human glioma cell lines. Among the many significant changes in glycogene expression observed, of particular interest was the observation that an additional α2,6-sialyltransferase, ST6 (α-N-acetyl-neuraminyl-2,3-β-galactosyl-1,3)-N-acetylgalactosaminide α2,6-sialyltransferase 5 (ST6GalNAcV), was expressed at very lowlevels in all glioma and glioma cell lines examined compared with normal brain. ST6GalNAcV catalyzes the formation of the terminal α2,6-sialic acid linkages on gangliosides. Stable transfection of ST6GalNAcV into U373MG gliomacells produced (i) no change in α2,6-linked sialic acid-containing glycoproteins, (ii) increased expression of GM2α and GM3 gangliosides and decreased expression of GM1b, Gb3, and Gb4, (iii) marked inhibition of in vitro invasivity, (iv) modified cellular adhesion to fibronectin and laminin, (v) increased adhesion-mediated protein tyrosinephosphorylationof HSPA8, and (vi) inhibition of tumor growth in vivo. These results strongly suggest that modulation of the synthesis of specific glioma cell-surface glycosphingolipids alters invasivity in a manner thatmay have significant therapeutic potential.

Original languageEnglish (US)
Pages (from-to)12646-12651
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number28
DOIs
StatePublished - Jul 13 2010
Externally publishedYes

    Fingerprint

Keywords

  • Glioblastoma
  • Glycosphingolipid
  • Glycosyltransferase
  • Glycosynapse
  • Heat shock 70 kDa protein 8

ASJC Scopus subject areas

  • General

Cite this