title: Overexpression of alpha1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splenic injection in athymic mice.
abstract: Changes in oligosaccharide structures alter the biological functions of cancer cells. Alpha1-6 fucosyltransferase (alpha1-6FucT) catalyzes the transfer of fucose to the innermost GlcNAc in N-glycans. Although alpha1-6FucT is barely detected in normal liver, it is enhanced during rat hepatocarcinogenesis and in human hepatoma. To understand the biological meaning of the alpha1-6FucT in hepatoma, especially in terms of metastasis, we established human hepatoma cell lines, which express high levels of alpha1-6FucT by transfection of the alpha1-6FucT gene and investigated intrahepatic metastasis after splenic injection to athymic mice. Tumor formation in the liver was dramatically suppressed in the alpha1-6FucT transfectants (1 of 9 and 1 of 10 in alpha1-6FucT transfectants versus 6 of 9 and 6 of 9 in controls). Although there were no differences in terms of cell invasiveness to a Matrigel or in terms of cytotoxicity to interleukin 2-treated lymphocytes between alpha1-6FucT transfectants and control cells, cell adhesion to mice hepatocytes and nonparenchymal liver cells in culture was significantly inhibited in alpha1-6FucT transfectants, compared to the controls. Attachment of alpha1-6FucT transfectants to a fibronectin-coated dish was decreased compared to controls because alpha5beta1 integrin was more strongly alpha1-6 fucosylated in the alpha1-6FucT transfectants. Two-dimensional electrophoresis followed by lectin blot showed that certain glycoproteins (Mr 50,000-150,000, pI 4.8-5.5) were alpha1-6 fucosylated and might be linked to suppression of intrahepatic metastasis. This is the first demonstration of the biological significance of alpha1-6 fucosylation on N-glycans in hepatoma cells under in vivo conditions.
authors.affiliation: Department of Biochemistry, Osaka University Medical School, Suita, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Miyoshi
authors.forename: K
authors.initials: K
authors.lastname: Noda
authors.forename: J H
authors.initials: JH
authors.lastname: Ko
authors.forename: A
authors.initials: A
authors.lastname: Ekuni
authors.forename: T
authors.initials: T
authors.lastname: Kitada
authors.forename: N
authors.initials: N
authors.lastname: Uozumi
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: N
authors.initials: N
authors.lastname: Matsuura
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007267:Injections; D007376:Interleukin-2 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D017469:Receptors, Fibronectin / Q000032:analysis; D013154:Spleen; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D007376:Interleukin-2; D009363:Neoplasm Proteins; D017469:Receptors, Fibronectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase