Developmental changes in carbohydrate moiety of human alpha‐fetoprotein

Abstract

Human AFP purified from fetal serum and amniotic fluid was separated into three different variants by chromatography on concanavalin A insolubilized on Sepharose (Con A--Sepharose). The three variants were indistinguishable in immunodiffusion and radioimmunoassay. Sera from patients with yolk-sac tumor and amniotic fluid from early pregnancy were found to contain a high proportion (15-45%) of AFP which does not bind to Con A, while AFP in fetal and newborn sera, and in amniotic fluid from late pregnancy, contained less (2-6%) of this variant. The use of a large excess of Con A--Sepharose and the fact that the non-bound AFP consistently eluted as non-bound in rechromatography showed that this AFP is non-reactive with Con A. Fractionation of radiolabelled AFP from cord serum in a mixture with amniotic fluid verified the difference in the amount of the Con-A nonreactive variant in AFP from these two sources. These results suggest that AFP synthesized by the yolk-sac tissue and by the liver are glycosylated differently. The variant may prove to be diagnostically useful.

Carbohydrate structures of human α-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans

“…Several investigators and we have reported that the reactivity of AFP with Lens culinaris agglutinin (LCA) and concanavalin A (Con A) is a good measure for distinction between HCC, nonneoplastic diseases of the liver and carcinomas of digestive organs which metastasise to the liver (Ruoslahti et al, 1978;Breborowicz et al, 1981;Ishiguro et al, 1985;Taketa & Hirai, 1989;Aoyagi et al, 1984Aoyagi et al, , 1991. The molecular basis for the different affinity of AFP for LCA and Con A is presumed to be the difference in fucosylation at the innermost N-acetylglucosamine residue and bisectingCorrespondence: Y.…”

Analysis of Lectin Affinity Immunoelectrophoretic Profiles of Serum Alpha-Fetoprotein from Patients with Yolk Sac Tumors and Carcinomas of the Gastrointestinal Tract: Correlations with Molecular Structures

“…Dambuyant et al 13] and Ruoslahti et al [14] first demonstrated the different reac tions of hepatoma AFP and of yolk sac tumor AFP with Con A, using the technique of affinity chromatography. Within a few years the technique of Con A affinity immu noelectrophoresis became more commonly used, and thereafter LCH affinity or phyto hemagglutinin E affinity immunoelectrophoresis of AFP was an important part of the tests, not only in the diagnosis of clinical patients [1][2][3][4][5] but also in the investigation of fetal organs [10,15].…”

“…The ratio of fucosylation may be related to the rapid tumor growth [12]. An N-acetylglucosamine residue linked (31,4 to the (3-linked man nose (bisect GlcNAc) was consistently present in the sugar chain of AFP of a yolk sac tumor grown in nude mice [7,8], but AFP in sera of patients with yolk sac tumor is considered to contain a sugar chain either with or without a bisect GlcNAc since the ratio of the Con A-nonreactive subfraction was about 50% in clinical samples [11,14], fucosylated sugar chain further contains a bisect GlcNAc molecule. Since this specula tion has not yet been fully studied, the fol lowing experimental work was undertaken.…”

4. Hepatocellular Cancer

“…The relative abundance of lentil lectin-reactive AFP in hepatocellular carci nomas has been shown by Breborowicz et al [14], Miyazaki et al [15] and Aoyagi et al [16], The appearance of concanavalin A (Con A)-nonreactive AFP in yolk sac tumors and extrahepatic malignancies has been doc umented by several investigators [14][15][16][17][18][19].…”