Specific detection of sialyl Lewis X determinant carried on the mucin GlcNAcβ1→6GalNAcα core structure as a tumor-associated antigen
Specific detection of sialyl Lewis X determinant carried on the mucin GlcNAcβ1→6GalNAcα core structure as a tumor-associated antigen
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DOI：
10.1006/bbrc.1998.8824
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发表时间：
1998-06-18
影响因子：
3.1
通讯作者：
Kannagi, R
中科院分区：
文献类型：
--
作者：
Kumamoto, K;Mitsuoka, C;Kannagi, R
唾液酸化刘易斯X作为选择素的配体，并被认为与癌症的血行转移有关。当用人岩藻糖基转移酶VI cDNA转染不表达唾液酸刘易斯X的培养的人乳腺癌细胞系MCF-7时，在转染细胞上诱导唾液酸刘易斯X的强表达。发现转染细胞也对抗体NCC-ST-439反应，其最初是针对人胃癌细胞产生的，后来显示出识别乳腺癌、胃癌和结肠癌中的肿瘤相关碳水化合物抗原。这表明NCC-ST-439识别的抗原与唾液酸刘易斯X密切相关。随后的研究表明，NCC-ST-439特异性地与NeuAc α 2->Gal β 1->4反应（Fuc α 1-->3）GlcNAc β 1--> 6 GalNAc α 1-->R，粘蛋白GlcNAc β 1-->6 GalNAc α结构上的唾液酸基刘易斯X，该抗体不与直链和/或支链聚乳糖胺结构上的常规唾液酸刘易斯X决定簇反应，包括Ne uAc α 2->3Gal β 1->4（Fuc α 1-->3）GlcNAc β 1-->3 Gal β 1-->4Glc β 1-->R和NeuAc α 2-3Gal β 1-->4（Fuc α 1-->3）GlcNAc β 1-->6Gal β 1--> 4Glc β 1-->R。这与大多数已知的抗唾液酸刘易斯X抗体形成鲜明对比，后者不会区分携带唾液酸刘易斯X决定簇的内部结构。另一方面，新产生的单克隆抗体GSC 154 -27的特异性与NCC-ST-439的特异性完全相反，因为它对直链和支链聚乳糖胺结构中的常规唾液酸刘易斯X决定簇具有强反应性，而对粘蛋白GrlcNAc β 1-> 6 GalNAc α核心结构上的唾液酸刘易斯X决定簇的反应性低得多。这两种抗体的一组可用于鉴别恶性细胞表达的唾液酸刘易斯X的分子种类，并研究其功能意义。(C)北京：科学出版社.
Sialyl Lewis X serves as a ligand for selectins and is proposed to be implicated in hematogenous metastasis of cancers. When a cultured human breast cancer cell line, MCF-7, which does not express sialyl Lewis X, was transfected with human fucosyltransferase VI cDNA, a strong expression of sialyl Lewis X was induced on transfectant cells, The transfectant cells were found to be also reactive to the antibody NCC-ST-439, which was initially raised against human gastric cancer cells and later was shown to recognize a tumor-associated carbohydrate antigen in breast, gastric, and colon cancers. This suggested that the antigen recognized by NCC-ST-439 is closely related to sialyl Lewis X, Subsequent studies indicated that NCC-ST-439 specifically reacts to NeuAc alpha 2-->Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc beta 1-->6GalNAc alpha 1-->R, the sialyl Lewis X on the mucin GlcNAc beta 1-->6 GalNAc alpha structure, The antibody was not reactive to the conventional sialyl Lewis X determinants on straight and/or branched polylactosamine structures including Ne uAc alpha 2-->3Gal beta 1-->4 (Fuc alpha 1-->3) GlcNAc beta 1-->3 Gal beta 1-->4Glc beta 1-->R and NeuAc alpha 2-3Gal beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->6Gal beta 1-->4 Glc beta 1-->R. This was in clear contrast to most of the known anti-sialyl Lewis X antibodies, which do not discriminate internal structures carrying the sialyl Lewis X determinant. On the other hand, the newly generated monoclonal antibody GSC154-27 had a specificity completely the reverse of the specificity of NCC-ST-439 in that it was strongly reactive to the conventional sialyl Lewis X determinants in straight and branched polylactosamine structures, while far less reactive to the sialyl Lewis X determinant on the mucin GrlcNAc beta 1-->6GalNAc alpha core structure. A set of these two antibodies would be useful in discriminating the molecular species of sialyl Lewis X expressed by malignant cells and in studying their functional significance. (C) 1998 Academic Press.