Alpha-fetoprotein-producing renal cell carcinoma with increased activity of N-acetylglucosaminyl-transferase III.
N-acetylglucosaminyltransferase (GnT) III catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin-A-(ConA)-reactive glycan into the ConA-nonreactive one. In this study, we measured GnT III levels in serum, tumor, and surrounding normal tissues together with a glucosaminylation index of alpha-fetoprotein (AFP), which is defined as the percentage of the ConA-nonreactive species in total AFP, in a case of AFP-producing renal cell carcinoma. The glucosaminylation index was determined by affinoelectrophoresis in the presence of ConA. GnT III was measured by using a pyridylaminated asialoagalactobiantennary sugar chain as a substrate by high-performance liquid chromatography. The glucosaminylation index of serum AFP, the concentration of which was 68 ng/ml, was 60%. This value is much higher than observed in hepatocellular carcinomas. The tumor tissue level of GnT III was 55.34 pmol/mg/h which was about six fold higher (9.50 pmol/mg/h) than in normal surrounding tissues. The serum level of this enzyme before surgery was 27.65 pmol/ml/h and decreased to 5.38 pmol/ml/h thereafter in association with a depression of serum AFP from 68 to 5.4 ng/ml. Thus, an increased level of GnT III in tumor tissues could account for the elevated conversion of a biantennary complex type sugar chain of AFP into a bisecting glucosaminylated biantennary one resulting from the addition of an N-acetylglucosamine residue at the trimannosyl core. This is, to our knowledge, the first report explaining the change in the carbohydrate structure of AFP with different affinity to ConA on the enzymatic basis in a renal cell carcinoma.
Aoyagi
Y
Y
Department of Internal Medicine, Niigata University School of Medicine, Japan.
Mori
S
S
Naitoh
A
A
Yanagi
M
M
Suzuki
Y
Y
Suda
T
T
Isokawa
O
O
Igarashi
H
H
Takahashi
T
T
Isemura
M
M
Asakura
H
H
D014408:Biomarkers, Tumor / Q000097:blood; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000097:blood*; D009392:Nephrectomy; D014057:Tomography, X-Ray Computed; D000509:alpha-Fetoproteins / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase