Kelleher P C, Walters C J, Myhre B D, Tennant B C, Gerin J L, Cote P J
Department of Medicine, University of Vermont, College of Medicine, Burlington 05405.
Cancer Lett. 1992 Apr 15;63(2):93-9. doi: 10.1016/0304-3835(92)90058-4.
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.
甲胎蛋白（AFP）糖基化改变已被认为是人类肝细胞癌（HCC）的一个标志物。研究土拨鼠AFP的凝集素结合特性，以确定土拨鼠肝炎病毒（WHV）诱导的肝癌是否也伴有AFP糖基化变化。来自正常、无WHV且AFP生理性升高的土拨鼠以及患有肝癌的WHV携带土拨鼠的AFP中，98%至100%与伴刀豆球蛋白A结合，这表明几乎所有的AFP都进行了糖基化。正常土拨鼠血清AFP与豆凝集素（LCA）结合的比例为3%或更低。相比之下，患有肝癌的土拨鼠的AFP与LCA结合的部分增加（范围为8%至77%）。WHV诱导的肝癌中LCA结合性AFP增加与人类乙型肝炎病毒（HBV）诱导的肝癌中常见的情况类似。这项研究证实了糖缀合物合成改变与病毒诱导的恶性转化之间的关系，确认了AFP糖型作为肝癌标志物的重要性，并表明感染WHV的土拨鼠在研究嗜肝DNA病毒肝癌发生和肝癌生长过程中AFP糖基化变化方面应具有重要作用。
