α2,6‐Sialyltransferase Gene Transfection into a Human Glioma Cell Line (U373 MG) Results in Decreased Invasivity

Yamamoto, Hirotaka; Kaneko, Yasunari; Rebbaa, Abdelhadi; Bremer, E.; Moskal, Joseph R.

doi:10.1046/j.1471-4159.1997.68062566.x

Cited by 42 publications

(40 citation statements)

References 20 publications

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“…High concentrations of GM3 also inhibit tumor cell invasion predominantly via interference with integrin receptor function, which would also be reflected in events downstream of the receptor. The predominant integrin in U373MG cells is α3β1, whose primary downstream effect is tyrosine phosphorylation of p125 FAK (5). We also did not observe adhesion-mediated alterations in p125 FAK expression in the transfectants.…”

Section: Discussionmentioning

confidence: 44%

“…Alteration in the composition of specific membrane domains, in turn, alters adhesivity to ECM components, increases the phosphorylation of HSPA8 protein, and decreases the invasive potential and in vivo tumorigenicity of glioma cells. Based on this and previous studies (3,5,6), modulating the expression of α2,6-sialic acids on either gangliosides or the N-linked oligosaccharides expressed on cell surface signaling molecules (i.e., integrins) by modulating glycogene expression may have therapeutic potential for the treatment of malignant gliomas.…”

Section: Discussionmentioning

confidence: 53%

“…Altered adhesivity of U373MG cells to fibronectin by modulation of cell surface N-linked glycoconjugates is mediated by altered tyrosine phosphorylation of p125 FAK (5). Regulation of laminin-mediated signaling in other systems has also been described (20).…”

Section: Resultsmentioning

confidence: 99%

“…The overexpression of the glycosyltransferase, GnT-V in gliomas, led to increased invasivity of these tumor cells in vitro, suggesting that β1,6-N-acetylglucosamine-bearing N-glycans play a role in glioma invasivity (3), consistent with earlier reports showing a strong correlation between metastatic potential and the expression of tri-and tetra-antennary β1,6NAG-bearing N-glycans (4). And recently, direct demonstration of a role for the oligosaccharide component of the glioma-associated integrin, α3β1, in regulating glioma invasivity has been reported (5,6).…”

mentioning

confidence: 99%

“…Interestingly, there is little to no α2,6-sialytransferase (ST6Gal1) activity, the enzyme that sialylates glycoprotein-associated, N-linked oligosaccharides, in malignant glioblastomas. Moreover, studies have shown that expression of this sialyltransferase in human glioma model systems inhibited both tumor growth and invasivity, by altering the signal transduction capability of the α3β1 integrin, because of its altered terminal sialic acid composition, and reflected in changes in focal adhesion kinase activity (5,6).…”

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confidence: 99%

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

Kroes

Emmett

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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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 low levels 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 glioma cells 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 tyrosine phosphorylation of 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 that may have significant therapeutic potential.glycosyltransferase | glycosphingolipid | glioblastoma | heat shock 70 kDa protein 8 | glycosynapse

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Section: Discussionmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Kroes

Emmett

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Overexpression of the α2,6 (N) sialyltransferase enzyme in human and rat neural cell lines is associated with increased expression of the polysialic acid epitope

Georgopoulou¹,

Breen²

1999

J. Neurosci. Res.

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The function of the neural cell adhesion molecule, NCAM, is modulated by the expression of the N-linked polysialic acid (PSA) oligosaccharide chain, with PSA serving to decrease the adhesive potential of the protein backbone. In this study, we have generated clonal cells of the rat B104 and human SH-SY5Y neuroblastoma cell lines that over-express the alpha2,6(N) sialyltransferase (ST6N) enzyme in order to investigate the role of this enzyme in PSA biosynthesis. The clonal cells exhibited ST enzyme activities of up to 20-times control levels, which remained stable throughout the duration of the study. The increase in enzyme activity paralleled an increase in enzyme protein levels, as determined by Western blot analysis, and immunocytochemical analysis confirmed the Golgi localisation of the enzyme. The induction of PSA-NCAM expression in the cells expressing high levels of ST6N was confirmed both by using anti-PSA antisera and by specific digestion with endo-N-acetylneuraminidase E, whose actions are specific for alpha2, 8-linked PSA chains. These results demonstrate that the cellular ST6N activity serves to positively influence the expression of PSA in neuronal cells.

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Protein Glycosylation and Cancer

Dennis

Granovsky

Ernst

et al. 2000

Carbohydrates in Chemistry and Biology

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α2,6‐Sialyltransferase Gene Transfection into a Human Glioma Cell Line (U373 MG) Results in Decreased Invasivity

Cited by 42 publications

References 20 publications

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

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

Overexpression of the α2,6 (N) sialyltransferase enzyme in human and rat neural cell lines is associated with increased expression of the polysialic acid epitope

Protein Glycosylation and Cancer

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