A secreted type of beta 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation: a novel function of GnT-V distinct from the original glycosyltransferase activity.
Angiogenesis is the first regulatory step of tumor progression. Herein, we report on some findings that show that beta1,6-N-acetylglucosaminyltransferase V (GnT-V) functions as an inducer of angiogenesis that has a novel and completely different function from the original function of glycosyltransferase. A secreted type of GnT-V protein itself promoted angiogenesis in vitro and in vivo at physiological concentrations. The highly basic domain of GnT-V induced the release of fibroblast growth factor-2 from heparan sulfate proteoglycan on the cell surface and/or extracellular matrix, leading to angiogenesis. These findings provide some novel information on the relationship between GnT-V and tumor metastasis. The inhibition of GnT-V secretion or its expression represents a novel potential strategy for the inhibition of tumor angiogenesis.
Saito
Takashi
T
Department of Biochemistry, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
Miyoshi
Eiji
E
Sasai
Ken
K
Nakano
Norihiko
N
Eguchi
Hironobu
H
Honke
Koich
K
Taniguchi
Naoyuki
N
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006031:Glycosylation; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism* / Q000502:physiology*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
D017077:Culture Media, Conditioned; D019812:Heparan Sulfate Proteoglycans; D010455:Peptides; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase