Glycomic analyses of glycoproteins in bile and serum during rat hepatocarcinogenesis.
Fucosylated alpha-fetoprotein (AFP) is a specific tumor marker for hepatocellular carcinomas (HCC). However, the mechanisms underlying the increase in fucosylated AFP in serum of patients with HCC are largely unknown. Recently, we reported that fucosylation is a possible signal for the secretion of glycoproteins into bile in the liver. This finding might lead to the selective secretion of fucosylated AFP into bile and the selective secretion might be disrupted in hepatocarcinogenesis. In this study, therefore, we analyzed the oligosaccharide structures of glycoproteins in bile and serum of LEC rats, which are a rat model of spontaneous hepatocarcinogenesis. Lectin microarraying showed enhanced binding of 13 lectins to bile, compared with in serum from normal LEC rats, and the binding of these lectins to serum of LEC rats bearing HCC was higher than in normal rats. Structural analyses involving HPLC and mass spectrometry showed that the fucosylation levels of serum glycoproteins were not increased in CH rats but were in HCC rats, although the fucosylation levels of biliary glycoproteins were increased in both CH and HCC rats. These results suggested that the sorting machinery through fucosylation might be disrupted in the liver with HCC.
Nakagawa
Tsutomu
T
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takeishi
Shunsaku
S
Kameyama
Akihiko
A
Yagi
Hirokazu
H
Yoshioka
Tomoko
T
Moriwaki
Kenta
K
Masuda
Tomomi
T
Matsumoto
Hitoshi
H
Kato
Koichi
K
Narimatsu
Hisashi
H
Taniguchi
Naoyuki
N
Miyoshi
Eiji
E
D000818:Animals; D001646:Bile / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005643:Fucose / Q000032:analysis; D054794:Glycomics / Q000379:methods*; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D013058:Mass Spectrometry; D009844:Oligosaccharides / Q000032:analysis; D011134:Polysaccharides / Q000032:analysis / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D051381:Rats; D020332:Rats, Inbred LEC
D006023:Glycoproteins; D037102:Lectins; D009844:Oligosaccharides; D011134:Polysaccharides; D005643:Fucose