Altered glycosylation of alpha-fetoprotein in hepadnavirus-induced hepatocellular carcinoma of the woodchuck.
Altered glycosylation of alpha-fetoprotein (AFP) has been proposed as a marker of hepatocellular carcinoma (HCC) in humans. The lectin-binding properties of woodchuck AFP were investigated to determine if woodchuck hepatitis virus (WHV)-induced HCCs are also accompanied by changes in AFP glycosylation. Ninety-eight to 100% of the AFP from normal, WHV-free woodchucks with physiologic AFP elevations and from WHV-carrier woodchucks with HCC bound to concanavalin A, indicating that virtually all of the AFP was glycosylated. Three percent or less of the serum AFP of normal woodchucks bound to Lens culinaris agglutinin (LCA). In contrast, the AFP from woodchucks with HCC had an increased LCA-binding fraction (range, 8-77%). The increased LCA-binding AFP in WHV-induced HCC is analogous to that which frequently accompanies hepatitis B virus (HBV)-induced HCC in humans. This study corroborates the relationship of altered glycoconjugate synthesis to virus-induced malignant transformation, confirms the importance of AFP glycoforms as markers of HCC, and demonstrates that the WHV-infected woodchuck should be useful in investigating changes in AFP glycosylation during hepadnavirus hepatocarcinogenesis and HCC growth.
Department of Medicine, University of Vermont, College of Medicine, Burlington 05405.
P C
PC
Kelleher
C J
CJ
Walters
B D
BD
Myhre
B C
BC
Tennant
J L
JL
Gerin
P J
PJ
Cote
D000818:Animals; D000831:Animals, Newborn; D014408:Biomarkers, Tumor / Q000032:analysis; D002846:Chromatography, Affinity; D003208:Concanavalin A / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D015613:Hepadnaviridae / Q000472:pathogenicity*; D037102:Lectins / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000382:microbiology*; D008297:Male; D008392:Marmota; D037121:Plant Lectins; D011863:Radioimmunoassay; D000509:alpha-Fetoproteins / Q000302:isolation & purification / Q000378:metabolism*
D014408:Biomarkers, Tumor; D037102:Lectins; D037121:Plant Lectins; D000509:alpha-Fetoproteins; C033619:lentil lectin; D003208:Concanavalin A