COP35, a Cholangiocarcinoma-Binding Oligopeptide, Interacts with the Clathrin Heavy Chain Accompanied by GRP78
COP35, a Cholangiocarcinoma-Binding Oligopeptide, Interacts with the Clathrin Heavy Chain Accompanied by GRP78
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DOI：
10.1158/1541-7786.mcr-10-0470
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发表时间：
2011-06-01
影响因子：
5.2
通讯作者：
Miyagawa, Shinichi
中科院分区：
文献类型：
--
作者：
Kitahara, Hiroe;Masumoto, Junya;Miyagawa, Shinichi
胆管癌（Cholangiocarcinoma， CCA）是一种常见的肝癌，由于缺乏有效的非手术治疗，加之其在诊断时进展迅速且不可操作，大多数患者预后较差。有效靶向CCA的新型非手术治疗方法的发展可以显著改善CCA患者的预后。在这里，我们描述了一种新的肽的迭代生产和表征，称为COP35 (CCA结合寡肽35)，它选择性地结合人CCA，通过噬菌体生物筛选，使用肝内CCA细胞系RBE和正常胆管细胞细胞系MMNK-1进行鉴定。发现COP35增强了5-氟尿嘧啶（5-FU）对RBE细胞的生长抑制作用。利用下拉法和液相色谱法，我们确定了GRP78/BiP伴生的网格蛋白重链是cop35的结合伙伴。总之，我们确定COP35是CCA肽靶向治疗的可能候选物。Mol - Cancer Res；9 (6);688 - 701。AACR (C) 2011。
Cholangiocarcinoma (CCA) is a common carcinoma of the liver, and the majority of patients with CCA have a poor prognosis due to the lack of effective nonsurgical therapies in addition to its rapid progression and inoperability at the time of diagnosis. The development of novel nonsurgical therapeutics that efficiently target CCA could significantly improve the prognosis for patients presenting with CCA. Here, we describe the iterative production and characterization of a novel peptide, designated COP35 (CCA-binding oligopeptide 35), which binds selectively to human CCA, identified by bacteriophage biopanning using the intrahepatic CCA cell line RBE and the normal cholangiocyte cell line MMNK-1. COP35 was found to augment the growth inhibitory effects of 5-fluorouracil (5-FU) against RBE cells. Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA. Mol Cancer Res; 9(6); 688-701. (C)2011 AACR.