Isolation of lung tumor specific peptides from a random peptide library: generation of diagnostic and cell-targeting reagents
Isolation of lung tumor specific peptides from a random peptide library: generation of diagnostic and cell-targeting reagents
复制标题
DOI：
10.1016/j.canlet.2003.08.011
复制
发表时间：
2003-12-30
期刊：
影响因子：
9.7
通讯作者：
Brown, KC
中科院分区：
文献类型：
--
作者：
Oyama, T;Sykes, KF;Brown, KC
在癌细胞表面发现特异性受体配体可能会影响临床问题，包括功能诊断和细胞特异性药物输送。利用噬菌体展示方法，我们分离出了与3种不同的人肺肿瘤细胞系NCI-H1299、NCI-H2009和A549结合的20-mer肽配体。平移方案是公正的，没有选择压力，以结合一个特定的细胞受体。分离的噬菌体与靶细胞的结合比对照噬菌体好24-300倍。此外，分离的肽显示出显著的细胞特异性，能够区分正常细胞和癌细胞以及不同的肺肿瘤细胞。细胞特异性与肿瘤类别不一致，表明肽能够识别肿瘤类型分类中未表示的细胞表面特征。分离的多肽在噬菌体环境外具有功能，多肽的多聚性增加了其对特定细胞类型的亲和力，从而扩大了其在临床中的应用。2003爱思唯尔爱尔兰有限公司版权所有。
Discovery of ligands specific to receptor(s) on a surface of a cancer cell could impact clinical issues including functional diagnosis and cell-specific drug delivery. Using a phage display approach, we have isolated 20-mer peptide ligands that bind to 3 different human lung tumor cell lines, NCI-H1299, NCI-H2009, and A549. The panning protocol is unbiased with no selection pressure towards binding a particular cellular receptor. The isolated phage bind to their target cells 24-300 times better than a control phage. Furthermore, the isolated peptides display remarkable cell-specificities and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. The cell-specificities are not coincident with tumor classes indicating that the peptides are able to recognize cell-surface features that are not represented within the classification of tumor type. The isolated peptides are functional outside of the context of the phage and multimerization of the peptide increases its affinity for its given cell type, thus expanding their utility in clinical situations. (C) 2003 Elsevier Ireland Ltd. All rights reserved.