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一种由单克隆抗体ACFH-18定义的新型肿瘤相关、发育调控糖脂抗原。

A novel tumor-associated, developmentally regulated glycolipid antigen defined by monoclonal antibody ACFH-18.

作者信息

Nudelman E D, Levery S B, Stroud M R, Salyan M E, Abe K, Hakomori S

机构信息

Biomembrane Institute, University of Washington, Seattle 98119.

出版信息

J Biol Chem. 1988 Sep 25;263(27):13942-51.

PMID:3417685
Abstract

A mouse IgM monoclonal antibody, ACFH-18, was established after immunization of mice with the human gastric cancer cell line MKN74. The antibody reacts strongly with gastrointestinal carcinoma and showed a clear dependence on the degree of differentiation of gastric cancer cells. The antibody defines a series of glycolipid species with extremely slow TLC mobility present in both acidic and neutral glycolipid fractions of the extract from gastrointestinal adenocarcinoma and the original MKN74 cells. Isolation and structural study of the active glycolipids present in the acidic and neutral fractions and comparison of the antibody reactivity with glycolipids having related structures revealed a novel specificity. The minimum requirement for the maximal reactivity of ACFH-18 was identified as VII3Fuc-nLc10 (Structure A below and Fig. 8 in text). Since the antibody did not react with III3Fuc-nLc6 (Structure B below), which shares the same terminal sequence as VII3Fuc-nLc10, and since it cross-reacted with VII3Fuc-nLc8 (Z1 glycolipid) and VII3Fuc,V3-Fuc,III3Fuc-nLc8 (Z3 glycolipid), antibody ACFH-18 is capable of recognizing a fucosyl residue plus an internal repeating N-acetyllactosamine proximal to ceramide, as indicated by lines in Fig. 8 (Structures A, B, and E-G). (Formula: see text).

摘要

用人类胃癌细胞系MKN74免疫小鼠后,建立了一种小鼠IgM单克隆抗体ACFH-18。该抗体与胃肠道癌强烈反应,并显示出对胃癌细胞分化程度的明显依赖性。该抗体定义了一系列在胃肠道腺癌和原始MKN74细胞提取物的酸性和中性糖脂组分中具有极慢TLC迁移率的糖脂种类。对酸性和中性组分中存在的活性糖脂进行分离和结构研究,并将抗体与具有相关结构的糖脂的反应性进行比较,揭示了一种新的特异性。ACFH-18最大反应性的最低要求被确定为VII3Fuc-nLc10(下文结构A和文中图8)。由于该抗体不与与VII3Fuc-nLc10具有相同末端序列的III3Fuc-nLc6(下文结构B)反应,并且由于它与VII3Fuc-nLc8(Z1糖脂)和VII3Fuc,V3-Fuc,III3Fuc-nLc8(Z3糖脂)发生交叉反应,如图8中的线所示(结构A、B和E-G),抗体ACFH-18能够识别岩藻糖基残基加上神经酰胺近端的内部重复N-乙酰乳糖胺。(公式:见正文)

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