The levels of fucosylated
glycoproteins in various
cancers and inflammatory processes have been a subject of intense study. The level of
fucosyltransferases and intracellular
GDP-L-
fucose, a
sugar nucleotide and a common donor substrate for all
fucosyltransferases, may regulate the level of fucosylated
glycoproteins. This study reports on the determination of
GDP-L-
fucose levels in human
hepatocellular carcinoma (HCC) and surrounding tissues, using a recently established high-throughput assay system. Levels of
GDP-L-
fucose in HCC tissues were significantly increased compared with adjacent nontumor tissues or normal livers. The mean +/- SD for
GDP-L-
fucose level was 3.6 +/- 0.2 micro mol/mg in control liver, 4.6 +/- 0.9 micro mol/mg in adjacent noninvolved liver tissues (
chronic hepatitis, 4.4 +/- 0.7 micro mol/mg;
liver cirrhosis, 4.8 +/- 0.9 micro mol/mg), and 7.1 +/- 2.5 micro mol/mg in HCC tissues. The level of
GDP-L-
fucose in HCC decreased in proportion with
tumor size (r = -0.675, P = 0.0002). When expression of the series of genes responsible for
GDP-L-
fucose synthesis was investigated, the gene expression of FX was found to be increased in 70% (7 of 10) of the HCC tissues examined compared with that in their surrounding tissues. The levels of
GDP-L-
fucose were positively correlated with the expression of FX
mRNA (r = 0.599, P = 0.0074). The levels of FX gene expression in some human
hepatoma and hepatocyte cell lines were determined. FX
mRNA production was strongly increased in HepG2 and Chang liver, moderately increased in Hep3B and HLF, and, in HLE, was similar to that of a normal human liver tissue. To investigate the effect of
GDP-L-
fucose on core fucosylation, FX
cDNA was transfected into Hep3B cells, which express a relatively low level of
GDP-L-
fucose:N-acetyl-beta-D-glucosaminide alpha1-6
fucosyltransferase (alpha1-6 FucT) and FX
mRNA. Transfection of this gene caused an increase in
GDP-L-
fucose levels as well as the extent of fucosylation on
glycoproteins, including
alpha-fetoprotein, as judged by reactivity to
lectins. Collectively, the results herein suggest that the high level of fucosylation in HCC is dependent on a high expression of FX followed by increases in
GDP-L-
fucose, as well as an enhancement in alpha1-6 FucT expression. Thus, an elevation in
GDP-L-
fucose levels and the up-regulation of FX expression represent potential markers for HCC.