SUGAR CHAINS OF HUMAN CORD SERUM ALPHA-FETOPROTEIN - CHARACTERISTICS OF N-LINKED SUGAR CHAINS OF GLYCOPROTEINS PRODUCED IN HUMAN LIVER AND HEPATOCELLULAR CARCINOMAS

Human serum alpha-fetoprotein (AFP) is elevated in not only hepatocell ular carcinoma (HCC) but also benign liver diseases. AFP produced in H CC and benign liver diseases was separated into several isoforms corre sponding to different sugar chain structures by several types of lecti n affinity electrophoresis, and the HCC-specific AFP isoform was discr iminated from those of benign liver diseases. Because a small amount o f HCC-specific AFP isoform was detected in cord serum AFP, the whole s ugar chain structures of human cord serum AFP were determined, as foll ows: beta1-->4GlcNAcbeta1-->2Manalpha1-->6(Neu5Acalpha2 ta1-->4GlcNAcb eta1-->2Manalpha1-->3)Manbeta1-->4R1 and R2, NAcbeta1-->2Manalpha1-->6 (Neu5Acalpha2-->6Galbeta1 -->4GlcNAcbeta1-->2Manalpha1-->3)Manbeta1--> 4R1 and R2, and beta1-->4GlcNAcbeta1-->2Manalpha1-->6(Neu5Acalpha2 ta1 -->4GlcNAcbeta1-->2Manalpha1-->3)Manbeta1-->4R1 and R2 in the ratio of 81.6:8.9:9.5. R1 and R2 denote GlcNAcbeta1-->4GlcNAc(OT) (subscript O T represents an (NaBH4)-H-3-reduced oligosaccharide) and GlcNAcbeta1-- >4(Fucalpha1-->6)GlcNAc(OT), respectively, and the ratio between R1 an d R2 in the respective fractions was approximately 19:1. In contrast, the sugar chain structure of HCC highly specific AFP isoform was found to comprise a monosialyl-biantennary sugar chain with additional fuco sylation of the proximal N-acetylglucosamine. Fucosylation of AFP prod uced in fetal liver increased in inverse proportion to the gestation p eriod, in weeks. indicating that fucosylation of AFP in HCC may be rel ated to the dedifferentiation of human hepatocytes through malignant t ransformation.