title: Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity.
abstract: The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.
authors.affiliation: The Chicago Institute of Neurosurgery and Neuroresearch, Illinois 60614, USA. cinnhiro@hotmail.com
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: J
authors.initials: J
authors.lastname: Swoger
authors.forename: S
authors.initials: S
authors.lastname: Greene
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: J
authors.initials: J
authors.lastname: Hurh
authors.forename: C
authors.initials: C
authors.lastname: Sweeley
authors.forename: J
authors.initials: J
authors.lastname: Leestma
authors.forename: E
authors.initials: E
authors.lastname: Mkrdichian
authors.forename: L
authors.initials: L
authors.lastname: Cerullo
authors.forename: A
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ihara
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: J R
authors.initials: JR
authors.lastname: Moskal
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011134:Polysaccharides / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C494041:ETS1 protein, human; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D011134:Polysaccharides; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; C067494:erythroagglutinating phytohemagglutinin; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase