Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapyof tumours
Altered glycosylation of proteins produced by malignant cells, and application for the diagnosis and immunotherapyof tumours
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DOI：
10.1111/j.1440-1711.2005.01351.x
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发表时间：
2005-08-01
影响因子：
4
通讯作者：
Amano, J
中科院分区：
文献类型：
--
作者：
Kobata, A;Amano, J
哺乳动物细胞产生的大多数分泌性和膜结合蛋白含有共价连接的糖链。糖蛋白的糖链结构的改变已被发现发生在各种肿瘤中。由于糖蛋白的糖链对于维持多细胞生物体中分化细胞的有序社会行为是必不可少的，糖链的改变是肿瘤细胞异常社会行为的分子基础，例如侵入周围组织和转移。本文介绍了在各种肿瘤中发现的N-连接糖链典型改变的结构和酶学基础，这些数据对设计肿瘤的诊断方法和临床治疗的免疫疗法是有用的。三种β-N-乙酰葡糖胺转移酶GnT-III、GnT-IV和GnT-V在多种肿瘤中复合型糖链的结构改变中起作用。此外，各种糖基转移酶的转录变化，以及负责形成复合型糖链外链部分的糖核苷酸和硫酸盐转运蛋白的转录变化，是诱导这些变化的关键。
Most secretory and membrane-bound proteins produced by mammalian cells containcovalently linked sugar chains. Alterations of the sugar chain structuresof glycoproteins have been found to occur in various tumours. Becausethe sugar chains of glycoproteins are essential for the maintenanceof the ordered social behaviour of differentiated cells in multicellularorganisms, alterations to the sugar chains are the molecular basisof abnormal social behaviours in tumour cells, such as invasioninto the surrounding tissues and metastasis. In this review, the structureand enzymatic basis of typical alterations of the N-linkedsugar chains, which are found in various tumours, are introduced.These data are useful for devising diagnostic methods and immunotherapiesfor the clinical treatment of tumours. Three beta-N-acetylglucosaminyltransferases,GnT-III, -IV and -V, play roles in the structural alteration of thecomplex-type sugar chains in various tumours. In addition, transcriptionalchanges in various glycosyltransferases, together with the transportersof sugar nucleotides and sulfate, which are responsible for theformation of the outer chain moieties of complex-type sugar chains,are the keys to inducing the alterations.