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Immunochemical studies of mucin-type glycoproteins

粘蛋白型糖蛋白的免疫化学研究

基本信息

批准号：
04454596
负责人：
YAMASHINA Ikuo
金额：
$ 4.1万
依托单位：
Faculty of Engineering, Kyoto Sangyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

To reveal the characteristic structures of mucins, mucin-specific monoclonal antibodies, MSW 113, MLS 102 and MLS 128, have been established. Using MSW 113, as an immunoaffinity agent, oligosaccharides have been isolated from human colostrum, all of which have the sialyl-Le^a determinant in linear and branched structures. Some of the oligosaccharides have the sialyl-Le^x determinant in addition to the sialyl-Le^a in the same molecule. These indicate that MSW 113 have a broad binding specificity.MSW 113 is in fact superior to NS 19-9, recognizing sialyl-Le^a structure specifically, in reacting with oligosaccharides having a variety of structures, which made MSW 113 a useful reagent to detect cancer antigens in sera of patients.Epitopes for MLS 102 and MLS 128, respectively, have been determined. MLS 102 is an anti-sialyl Tn antibody. From ovine submaxillary mucin (OSM), glycopeptides with a cluster structure, composed of Sia-GalNAc-Ser/Thr, have been isolated. After the removel of sialic acid, the glycopeptides turned out to be the epitope for MLS 128, an anti-Tn antibody. The cluster structure composed of three or four consecutive sequences of GalNAc-Ser/Thr was initially found in OSM,but similar clusters have then been found in Tn-glycophorin A from Tn erythrocyte and leukosialin from a T-lymphoid cell, Jurkat.Sialyl Tn and Tn antigens have been regarded as tumor marker. In fact, MLS 102 and MLS 128 are effective in staining histochemically cancer tissues, thus being potentially candidates for in vivo imaging agents for cancer patients.Mucins were isolated from cancer cells and pleural fluids from cancer patients and their carbohydrate moieties were analyzed. Like OSM,these mucins express at least both sialyl Tn and Tn antigens. The factors which determine the co-expression of these two antigens remain unknown, since the co-expression occurs in the circumstance where sugar transferases including sialyl transferase occur.

为了揭示粘蛋白的特征结构，已经建立了粘蛋白特异性单克隆抗体MSW 113、MLS 102和MLS 128。使用MSW 113作为免疫亲和剂，已从人初乳中分离出寡糖，所有这些寡糖都具有线性和分支结构的唾液酸-Le ^a决定簇。一些寡糖在同一分子中除了唾液酸-Le ^a之外还具有唾液酸-Le ^x决定簇。MSW 113与多种结构的寡糖反应，特异性识别唾液酸-Le_a结构，是一种上级NS 19-9的特异性结合抗原的试剂，可用于检测患者血清中的癌抗原，并测定了MLS 102和MLS 128的抗原表位。MLS 102是抗唾液酸Tn抗体。从绵羊颌下粘蛋白（OSM）中分离到了一种由Sia-GalNAc-Ser/Thr组成的簇状结构的糖肽。在去除唾液酸后，糖肽被证明是抗Tn抗体MLS 128的表位。最初在OSM中发现了由三个或四个连续的GalNAc-Ser/Thr序列组成的簇结构，但随后在Tn红细胞的Tn血型糖蛋白A和T淋巴细胞的白唾液酸中发现了类似的簇结构。唾液酸Tn和Tn抗原被认为是肿瘤标志物。事实上，MLS 102和MLS 128在组织化学染色癌组织中是有效的，因此是用于癌症患者的体内成像剂的潜在候选物。与OSM一样，这些粘蛋白至少表达唾液酸化Tn和Tn抗原。决定这两种抗原的共表达的因素仍然未知，因为共表达发生在糖转移酶（包括唾液酸转移酶）发生的情况下。