Characterization of Novel Carbohydrate Ligands for Serum Lectin Associated with Anti-tumor Activity

与抗肿瘤活性相关的血清凝集素新型碳水化合物配体的表征

基本信息

批准号：
16590046
负责人：
KAWASAKI Nobuko
金额：
$ 2.3万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590046/
关键词：
Mannan-binding protein Mannose-binding protein Serum lectin Human colon cancer cell Carbohydrate ligands Fucosylated polylactosamine structure CD26 Anti-tumor activity ヒト結腸がん細胞 CD98 heavy chain ポリラクトサミン糖鎖ルイス型抗原

项目摘要

Mannan-binding protein (MBP) is a C-type mammalian lectin specific for Man, GlcNAc, and Fuc. The serum MBP has a potent growth inhibitory activity to a human colorectal carcinoma cell line in vivo via a complement-independent mechanism. In this study, we isolated and characterized the carbohydrate ligands to MBP expressed on the SW1116 cells, which were assumed to be associated with the anti-tumor activity of MBP.1. Isolation and characterization of the MBP-ligand oligosaccharides.By MS analyses of the MBP-ligand oligosaccharides and their endo-β-galactosidase digested products in combination with1) The non-reducing terminal unit of the MBP-ligand oligosaccharides is mostly Lewis a/b, a substantial portion of which is carried on extended type 1 chains as multimeric Lewis a units.2) The core portion of the oligosaccharides consisted mostly of core fucosylated tetra-antennary N-glycans.3) The inner units are most likely to be dominated by type 2 chain and not fully fucosylated.The overal … More l charbohydrate structures of neutral and acidic MBP-ligands are very similar except for the non-reducing termini. The acidic ligands are capped with sialic acid to form sialyl Lewis a structure. The MBP-oligosaccharide ligands expressed on human colon carcinoma, SW1116, cells, were large N-glycans with a highly fucosylated polylactosamine-type structures. These structures were unique and distinct from other previously reported tumor specific carbohydrate antigens. MBP requires clusters of tandem repeats of the Lewis a epitope for the binding.2. Isolation and characterization of the glycoproteins carrying the MBP-ligand oligosaccharides of the characteristic structure.1) The cell surface MBP-ligand glycoproteins, which had been labeled with biotin, were isolated by MBP- and avidin-affinity columns. A 120 kDa band on SDS-PAGE under reducing conditions was detected as a major component. The protein lost most of the binding activity to MBP by N-glycanase digestion.2) The MBP-ligand glycoproteins isolated by AAL- and MBP-affinity columns from SW1116 cell lysates. Two major bands, 120kDa and 82kDa on SDS-PAGE under reducing conditions were identified as CD26 and CD98 heavy chain, respectively, by MS analysis. Less

Mannan结合蛋白（MBP）是针对人，GlcNAC和FUC的C型哺乳动物讲座。血清MBP通过与补体无关的机制在体内对人体有色癌细胞系具有潜在的生长抑制活性。在这项研究中，我们将碳水化合物配体分离为在SW1116细胞上表达的MBP，这被认为与MBP.1的抗肿瘤活性有关。 Isolation and Characterization of the MBP-ligand oligosaccharides.By MS analyses of the MBP-ligand oligosaccharides and their endo-β-galactosidase digested products in combination with1) The non-reducing terminal unit of the MBP-ligand oligosaccharides is mostly Lewis a/b, a substantial portion of which is carried on extended type 1 chains as multimediary 2）寡糖的核心部分主要由核心基化的四年级n-glycans组成。3）内部单元最有可能由2型链中主导，而不是完全葡萄糖基化。除非还原末端外，总的中性和酸性MBP配体的含L型结构结构非常相似。酸性配体用唾液酸覆盖以形成siallyl刘易斯的结构。在人类结肠癌（SW1116）中表达的MBP-寡糖配体是具有高度葡萄糖基化的果胶类胺型结构的大型N-聚糖。这些结构是独一无二的，与其他先前报道的肿瘤特异性碳水化合物抗原不同。 MBP需要刘易斯的串联重复群，是结合的表位。2。携带特征结构的MBP - 配体寡糖的糖蛋白的分离和表征。1）通过MBP-和Avidin-birinity-bilition柱分离的细胞表面MBP-cligand糖蛋白被标记为生物素。在还原条件下，SDS-PAGE上的120 kDa频段被视为主要组成部分。该蛋白质通过N-糖化酶消化失去了与MBP的大部分结合活性。2）由SW1116细胞裂解物中的AAL-和MBP - 亲和力柱分离的MBP - 配体糖蛋白。通过MS分析，在还原条件下，SDS-PAGE上的两个主要频带分别为CD26和CD98重链，在SDS-PAGE上的两个主要频段和82KDA。较少的

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of carbohydrate ligands recgnized by mannan-binding protein on SW1116 cells.

SW1116 细胞上甘露聚糖结合蛋白识别的碳水化合物配体的表征。

DOI：
发表时间：
2005
期刊：
Glycobiology 15(11)
影响因子：
0
作者：
M.Morishita;T.Goto;K.Nakamura;A.M.Lowman;K.Takayama;N.A.Peppas;Mori M.et al.;N.Kawasaki
通讯作者：
N.Kawasaki

Mannan-binding protein blocks the activation of metalloproteases meprin α and β