MUC1 mucin core protein binds to the domain 1 of ICAM-1

MUC1 mucin core protein binds to the domain 1 of ICAM-1
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DOI:
10.1159/000051917
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发表时间:
2001-01-01
期刊:
影响因子:
3.2
通讯作者:
Imai, K
Imai, K
中科院分区:
医学3区
文献类型:
--
作者:
Hayashi, T;Takahashi, T;Imai, K

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背景资料:MUC 1在多种上皮性肿瘤中异常表达,我们已经报道MUC 1在从原发部位分离、侵入间质组织和保护免疫应答中起重要作用。本研究的目的是确定MUC 1与细胞间粘附分子1(ICAM-1)的精确结合,加速癌症转移。方法:采用细胞聚集实验检测MUC 1cDNA转染细胞与ICAM-1表达细胞的聚集情况。将抗MUC 1抗体、抗ICAM-1抗体或MUC 1核心蛋白的合成肽加入到测定中以抑制细胞聚集。结果:MUC 1:转染细胞的聚集率显著高于对照细胞。这种聚集通过抑制O-聚糖生物合成而进一步增强。它被识别MUC 1核心蛋白的串联重复结构域的抗MUC 1抗体或识别结构域1的抗ICAM-1抗体抑制。它也被合成MUC 1肽的40个氨基酸对应于两个串联重复抑制。结论:结果显示,MUC 1粘蛋白核心蛋白的串联重复结构域与ICAM-1的结构域1结合,提示MUC 1-ICAM-1相互作用在上皮性肿瘤转移中的潜在作用。版权所有(C)2001 S. Karger AG,巴塞尔。
Background: MUC1 is aberrantly expressed on a variety of epithelial tumors, We have reported that MUC1 plays important roles in separation from primary site, invasion into the stromal tissue, and protection from immune responses. The aim of this study is to determine the precise binding of MUC1 to intercellular adhesion molecule 1 (ICAM-1) that accelerates the cancer metastasis. Methods: A cell aggregation assay between MUC1 cDNA transfectants and ICAM-1 expressing cells was employed. An anti-MUC1 antibody, anti-ICAM-1 antibody or synthetic peptide of MUC1 core protein was added to the assay to inhibit the cell aggregation. Results: MUC1: transfectants showed a significantly higher aggregation rate compared to the control cells. Th is aggregation was further enhanced by the inhibition of O-glycan biosynthesis. It was inhibited by either an anti-MUC1 antibody recognizing the tandem repeat domain of MUC1 core protein or an anti-ICAM-1 antibody identifying domain 1. It was also inhibited by a synthetic MUC1 peptide of 40 amino acids corresponding to two tandem repeats. Conclusions: The results revealed that a tandem repeat domain of MUC1 mucin core protein binds to domain 1 of ICAM-1, suggesting a potential role of MUC1-ICAM-1 interaction in the metastasis of epithelial tumors. Copyright (C) 2001 S. Karger AG, Basel.