Isolation of a colon tumor specific binding peptide using phage display selection
Isolation of a colon tumor specific binding peptide using phage display selection
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DOI：
10.1016/s1476-5586(03)80046-5
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发表时间：
2003-09-01
期刊：
影响因子：
4.8
通讯作者：
Jones, DA
中科院分区：
文献类型：
--
作者：
Kelly, KA;Jones, DA
结直肠癌是美国第三大常见恶性肿瘤。提高早期结直肠肿瘤的检测灵敏度将具有重要的临床应用价值。在此，我们报告使用噬菌体展示产生的肽库，检测结肠癌组织。为了实现这一点，我们采用了对低分化结肠癌细胞（HT 29）的携带肽的噬菌体文库的阳性选择，并将其与对高分化结肠癌细胞（HCT 116）的噬菌体文库的阴性选择相结合。对所得文库的分析鉴定了染色HT 29结肠癌细胞的九个氨基酸的二硫键约束肽CPIEDRPMC（RPMrel）。使用FITC缀合的RPMrel肽的免疫组织化学染色也显示RPMrel与来自四名患者的结肠肿瘤组织的结合。我们没有看到RPMrel与正常结肠组织结合。此外，RPMrel未能染色一组非结肠组织，包括肺、肝和胃。我们进一步证明了RPMrel与线粒体毒素（KLAKLAK）偶联（2）杀死HT 29细胞。这些研究表明，RPMrel可能是一个有前途的领导候选人在发展一个有用的结肠肿瘤诊断和靶向药物输送剂。
Colorectal cancer is the third most common malignancy in the United States. Improved detection sensitivity of early colorectal neoplasms would have important clinical applications. Herein, we report on using phage display to generate peptide libraries that detect colon carcinoma tissues. To accomplish this, we employed positive selection of a peptide-bearing phage library on poorly differentiated colon carcinoma cells (HT29) and combined this with negative selection of the phage library on well-differentiated colon carcinoma cells (HCT116). Analysis of the resulting library identified a nine-amino-acid, disulfide-constrained peptide, CPIEDRPMC (RPMrel), that stained HT29 colon carcinoma cells. Immunohistochemical staining using FITC-conjugated RPMrel peptide also showed binding of RPMrel to colon tumor tissues from four patients. We saw no binding of RPMrel to normal colon tissues. In addition, RPMrel failed to stain a panel of noncolon tissues including the lungs, liver, and stomach. We further demonstrated that RPMrel coupled to the mitochondrial toxin (KLAKLAK)(2) killed HT29 cells. These studies suggest that RPMrel may be a promising lead candidate in the development of a useful colon tumor diagnostic and targeted drug delivery agent.