Overexpression of alpha1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splenic injection in athymic mice.
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.
Miyoshi
E
E
Department of Biochemistry, Osaka University Medical School, Suita, Japan.
Noda
K
K
Ko
J H
JH
Ekuni
A
A
Kitada
T
T
Uozumi
N
N
Ikeda
Y
Y
Matsuura
N
N
Sasaki
Y
Y
Hayashi
N
N
Hori
M
M
Taniguchi
N
N
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
D015820:Cadherins; D007376:Interleukin-2; D009363:Neoplasm Proteins; D017469:Receptors, Fibronectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase