GLYCOLIPID CORE STRUCTURE SWITCHING FROM GLOBO-SERIES TO LACTO-SERIES AND GANGLIO-SERIES DURING RETINOIC ACID-INDUCED DIFFERENTIATION OF TERA-2-DERIVED HUMAN EMBRYONAL CARCINOMA-CELLS
GLYCOLIPID CORE STRUCTURE SWITCHING FROM GLOBO-SERIES TO LACTO-SERIES AND GANGLIO-SERIES DURING RETINOIC ACID-INDUCED DIFFERENTIATION OF TERA-2-DERIVED HUMAN EMBRYONAL CARCINOMA-CELLS
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DOI：
10.1016/0012-1606(87)90328-9
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发表时间：
1987-07-01
影响因子：
2.7
通讯作者：
HAKOMORI, SI
中科院分区：
文献类型：
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作者：
FENDERSON, BA;ANDREWS, PW;HAKOMORI, SI
我们分析了最近克隆的人胚胎癌 (EC) 细胞系 NTERA-2 的糖脂标记物，该细胞系在接触视黄酸时广泛分化为多种体细胞类型。这些肿瘤细胞提供了一个模型系统，可用于研究人类胚胎发育过程中糖脂多样性的个体发育。使用一套全面的抗碳水化合物单克隆抗体，通过细胞表面免疫荧光和薄层层析免疫染色来鉴定糖脂抗原。未分化的 NTERA-2 细胞被发现主要表达 globo 系列糖脂，包括 Gb3、Gb5 (IV3GalGb4)、globo-ganglioside (IV3NeuAc.alpha.2 .fwdarw. 3GalGb4)、globo-H (IV3Fuc.alpha.1 .fwdarw. 2GalGb4) 和 globo-A (IV3GalNAc.alpha.1.fwdarw.3[Fuc.alpha.1.fwdarw.2]GalGb4)。当 NTERA-2 细胞在 10-5 M 视黄酸存在下培养诱导分化时，观察到细胞糖脂从球系列向乳糖系列和神经节系列发生显着转变：球系列结构下降，特别是在首次暴露于视黄酸后 7-20 天期间，而乳系列结构，包括岩藻糖基.α.1 .fwdarw。 3型2链(Lex)和唾液酸基2型链以及神经节系列结构，包括GM3、GD3、9-O-乙酰基-GD3、GM2、GD2和GT3增加。未分化 NTERA-2 细胞中 globo-A 和 globo-H 作为主要 ABH 血型抗原的存在表明 globo 系列血型抗原是胚胎抗原，其合成在人类发育过程中转变为乳系列。双色免疫荧光分析表明，几种神经节系列和乳系列抗原在不同的分化细胞亚群上优先表达，并允许确定这些亚群与 NTERA-2 培养物中神经元发育的关系。结果表明，糖基转移酶，特别是那些参与控制复合糖核心结构组装的糖基转移酶，是人类 EC 细胞分化过程中以及人类胚胎发生过程中受调节的关键酶。
We have analyzed the glycolipid markers of a recently cloned human embryonal carcinoma (EC) cell line, NTERA-2, which differentiates extensively into a variety of somatic cell types when exposed to retinoic acid. These tumor cells provide a model system that can be used to study the ontogeny of glycolipid diversity during human embryonic development. Glycolipid antigens were identified by cell surface immunofluorescence and thin-layer chromatography immunostaining using a comprehensive set of anticarbohydrate monoclonal antibodies. Undifferentiated NTERA-2 cells were found to express predominantly globo-series glycolipids, including Gb3, Gb5 (IV3GalGb4), globo-ganglioside (IV3NeuAc.alpha.2 .fwdarw. 3GalGb4), globo-H (IV3Fuc.alpha.1 .fwdarw. 2GalGb4), and globo-A (IV3GalNAc.alpha.1 .fwdarw. 3[Fuc.alpha.1 .fwdarw. 2]GalGb4). When NTERA-2 cells were induced to differentiate by culturing in the presence of 10-5 M retinoic acid, a remarkable shift of cellular glycolipids from globo-series to lacto- and ganglio-series was observed: Globo-series structures declined, particularly during the period 7-20 days after first exposure to retinoic acid, while lacto-series structures, including fucosyla.alpha.1 .fwdarw. 3 type 2 chain (Lex) and sialosyl type 2 chain, and ganglio-series structures, including GM3, GD3, 9-O-acetyl-GD3, GM2, GD2, and GT3 increased. The presence of globo-A and globo-H as the major ABH blood group antigens in undifferentiated NTERA-2 cells suggests that globo-series blood group antigens are embryonic antigens, synthesis of which switches to lacto-series during human development. Two-color immunofluorescence analysis indicated preferential expression of several ganglio- and lacto-series antigens on different subsets of differentiated cells and permitted the relationship of these subsets to the development of neurons in NTERA-2 cultures to be determined. The results suggest that glycosyltransferases, particularly those involved in controlling glycoconjugate core structure assembly, are key enzymes regulated during the differentiation of human EC cells and, by implication, during human embryogenesis.