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Overexpression of 1-6 Fucosyltransferase in Hepatoma Cells Suppresses Intrahepatic Metastasis after Splenic Injection in Athymic Mice¹

Departments of Biochemistry [E. M., K. N., J. H. K., A. E., T. K., N. V., Y. I., N. T.] and Internal Medicine and Therapeutics [E. M., K. N., Y. S., N. H., M. H.], Osaka University Medical School, and Department of Pathology, Allied Health Science, Osaka University Faculty of Medicine [N. M.], Osaka 565-0871, Japan

Changes in oligosaccharide structures alter the biological functions of cancer cells. 1-6 fucosyltransferase (1-6FucT) catalyzes the transfer of fucose to the innermost GlcNAc in N-glycans. Although 1-6FucT is barely detected in normal liver, it is enhanced during rat hepatocarcinogenesis and in human hepatoma. To understand the biological meaning of the 1-6FucT in hepatoma, especially in terms of metastasis, we established human hepatoma cell lines, which express high levels of 1-6FucT by transfection of the 1-6FucT gene and investigated intrahepatic metastasis after splenic injection to athymic mice. Tumor formation in the liver was dramatically suppressed in the 1-6FucT transfectants (1 of 9 and 1 of 10 in 1-6FucT 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 1-6FucT transfectants and control cells, cell adhesion to mice hepatocytes and nonparenchymal liver cells in culture was significantly inhibited in 1-6FucT transfectants, compared to the controls. Attachment of 1-6FucT transfectants to a fibronectin-coated dish was decreased compared to controls because 5ß1 integrin was more strongly 1-6 fucosylated in the 1-6FucT transfectants. Two-dimensional electrophoresis followed by lectin blot showed that certain glycoproteins (M_r 50,000–150,000, pI 4.8–5.5) were 1-6 fucosylated and might be linked to suppression of intrahepatic metastasis. This is the first demonstration of the biological significance of 1-6 fucosylation on N-glycans in hepatoma cells under in vivo conditions.

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