Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines - Demonstration of simpler and fewer glycan chains in tumor cells
Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines - Demonstration of simpler and fewer glycan chains in tumor cells
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DOI：
10.1074/jbc.271.52.33325
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发表时间：
1996-12-27
影响因子：
4.8
通讯作者：
TaylorPapadimitriou, J
中科院分区：
文献类型：
--
作者：
Lloyd, KO;Burchell, J;TaylorPapadimitriou, J
与来自相应正常组织的粘蛋白相比，MUC-1粘蛋白被认为在乳腺癌、卵巢癌和其他癌中异常糖基化。为了阐明糖基化中的这些差异，我们比较了从[H-3] GlcN标记的乳腺上皮细胞系（MMSV 1 -1、MTSV 1 -7和HB-2）免疫沉淀的MUC-1的O-连接的糖链，这些细胞系来源于从人乳培养的细胞，与三种乳腺癌细胞系（MCF-7、BT-20和T47 D）。高pH阴离子色谱分析表明，正常细胞系比癌细胞系具有更高的GlcN/GalN比例和更复杂的寡糖谱。对来自MTSV 1 -7和T47 D MUC-1的寡糖进行了结构分析，并提出了以下结构。T47 D的MUC-1具有相当简单的糖基化模式，以NeuAc α 2-3Gal β 1- 3GalNAc-醇、Gal β 1- 3GalNAc-醇和GalNAc-醇为主;相反，来自MTSV 1 -7的MUC-1具有更复杂的结构，包括许多二唾液酸基，核心2种类，即NeuAc α 2- 3Gal β 1-4GlcNAc β 1-6[NeuAc α 2-3Gal β 1-3] GalNAc-醇和NeuAc α 2-3Gal β 1-4GlcNAc β 1-6[NeuAc α 2-3Gal β 1- 4GlcNAc β 1-3Gal β 1-3] GalNAc-醇。用[H-3]GlcN和C-14-氨基酸的双标记实验和MUC-1中GalNAc或GalNAc-醇：蛋白质比率的分析表明，两种细胞类型之间的粘蛋白的糖基化程度也存在显著差异。我们的结论是，从乳腺癌细胞系MUC-1有更简单，更少，碳水化合物链比MUC-1从正常乳腺上皮细胞，这些差异，组合或单独，解释了一些MUC-1抗体和T细胞的差异肿瘤特异性。
MUC-1 mucin is considered to be aberrantly glycosylated in breast, ovary, and other carcinomas in comparison with mucin from corresponding normal tissues. In order to clarify these differences in glycosylation, we have compared the O-linked carbohydrate chains from MUC-1 immunoprecipitated from [H-3]GlcN-labeled breast epithelial cell Lines (MMSV1-1, MTSV1-7, and HB-2) derived from cells cultured from human milk, with three breast cancer cell lines (MCF-7, BT-20, and T47D). Analysis by high pH anion chromatography showed that the normal cell lines had a higher ratio of GlcN/GalN and more complex oligosaccharide profiles than the cancer cell lines. Structural analyses were carried out on the oligosaccharides from MTSV1-7 and T47D MUC-1, and the following structures were proposed. MUC-1 from T47D had rather a simple glycosylation pattern, with NeuAc alpha 2-3Gal beta 1-3GalNAc-ol, Gal beta 1-3GalNAc-ol, and GalNAc-ol predominating; in contrast, MUC-1 from MTSV1-7 had more complex structures, including a number of disialo, core 2 species, i.e. NeuAc alpha 2-3 Gal beta 1-4GlcNAc beta 1-6[NeuAc alpha 2-3Gal beta 1-3]GalNAc-ol and NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-6[NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-3]GalNAc-ol. Double-labeling experiments with [H-3]GlcN and C-14-aminoacids and analysis of GalNAc or GalNAc-ol:protein ratios in MUC-1 showed that there was also a significant difference in the degree of glycosylation of the mucin between the two cell types. We conclude that MUC-1 from breast cancer cell lines has simpler, and fewer, carbohydrate chains than MUC-1 from normal breast epithelial cells, and that these differences, combined or separately, explain the differential tumor specificity of some MUC-1 antibodies and T cells.