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抑制结肠癌细胞与E-选择素结合的新型糖蛋白。

Novel glycoproteins inhibiting the binding of colorectal cancer cells to E-selectin.

作者信息

Inoue M, Nakada H, Oka Y, Tanaka N, Yamashina I

机构信息

Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Japan.

出版信息

Glycoconj J. 1997 Jan;14(1):147-53. doi: 10.1023/a:1018529419094.

DOI:10.1023/a:1018529419094
PMID:9076523
Abstract

Novel glycoproteins carrying sialyl-LeA (SLeA) antigens (SL-GP) were isolated from ascites fluid from a patient with colorectal cancer by immunoaffinity chromatography. Their characteristics, including binding capacity to E-selectin, were investigated. SL-GP showed a typical mucin type amino acid composition in which Ser, Thr and Pro together accounted for greater than 50% of the total amino acid residues. A large amount of carbohydrate (about 80%) was present in SL-GP. The number of O-glycans carrying SLeA antigens comprised about 9% of the total number of O-glycosidic chains. SL-GP could bind to IL-1 beta treated HUVEC, and the binding was inhibited by anti-E-selectin and anti-SLeA monoclonal antibodies. The binding of colorectal cancer cells, LS 180, to HUVEC was assayed in the presence of SL-GP, oligosaccharides prepared from SL-GP and human milk SLeA hexasaccharide. SL-GP inhibited the binding most effectively, whereas equivalent amounts of the SL-GP oligosaccharides and milk SLeA hexasaccharide inhibited it only slightly. These results constitute direct evidence that a unique arrangement of SLeA antigens on the polypeptide chain, probably a cluster, is essential for the binding to E-selectin.

摘要

通过免疫亲和层析从一名结直肠癌患者的腹水中分离出携带唾液酸化岩藻糖基乳糖(SLeA)抗原的新型糖蛋白(SL-GP)。研究了它们的特性,包括与E-选择素的结合能力。SL-GP显示出典型的粘蛋白型氨基酸组成,其中丝氨酸、苏氨酸和脯氨酸 together 占总氨基酸残基的50%以上。SL-GP中存在大量碳水化合物(约80%)。携带SLeA抗原的O-聚糖数量约占O-糖苷链总数的9%。SL-GP可与白细胞介素-1β处理的人脐静脉内皮细胞(HUVEC)结合,且这种结合被抗E-选择素和抗SLeA单克隆抗体抑制。在SL-GP、由SL-GP制备的寡糖和人乳SLeA六糖存在的情况下,检测结直肠癌细胞LS 180与HUVEC的结合。SL-GP抑制结合的效果最显著,而等量的SL-GP寡糖和乳SLeA六糖仅轻微抑制结合。这些结果构成了直接证据,表明SLeA抗原在多肽链上的独特排列,可能是一个簇,对于与E-选择素的结合至关重要。

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本文引用的文献

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Characterization of a specific ligand for P-selectin on myeloid cells. A minor glycoprotein with sialylated O-linked oligosaccharides.髓系细胞上P-选择素特异性配体的鉴定。一种带有唾液酸化O-连接寡糖的小分子糖蛋白。
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