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从噬菌体展示肽库中鉴定与结肠癌细胞特异结合的肽。

Identification of a specific peptide binding to colon cancer cells from a phage-displayed peptide library.

机构信息

Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

Department of Gastroenterology, Shanghai General Hospital, Shanghai 200060, China.

出版信息

Br J Cancer. 2018 Jan;118(1):79-87. doi: 10.1038/bjc.2017.366. Epub 2017 Oct 24.

Abstract

BACKGROUND

New molecular probes are essential for early colon cancer diagnosis. A phage-display screening was performed to select novel binding peptides for early colon cancer imaging detection.

METHODS

A human colon cancer cell line (COLO320HSR) and a normal human intestinal epithelial cell line (NCM460) were used for subtractive screening with a phage peptide library. The positive peptides were identified, and their binding capacities were confirmed by confocal immunofluorescence both in human colon cancer cells and in biopsy specimens. The sequences were further analysed for homology and the existing mimotopes by the BLAST algorithm and the MimoDB database.

RESULTS

A peptide termed as CBP-DWS, which was demonstrated to be capable of binding to a panel of human colon cancer cell lines and tissues, was identified; it had virtually no binding to normal human intestinal epithelial cell line NCM460 and normal surrounding colon tissues. Bioinformatics analyses suggest that CBP-DWS targets human Glypican-3, which may be involved in important cellular functions in multiple cancer types.

CONCLUSIONS

These studies suggest that the selected peptide CBP-DWS may be a candidate to serve as a novel probe for colon cancer imaging.

摘要

背景

新的分子探针对于早期结肠癌的诊断至关重要。本研究采用噬菌体展示技术筛选用于早期结肠癌成像检测的新型结合肽。

方法

用人结肠癌细胞系(COLO320HSR)和正常的人肠道上皮细胞系(NCM460)进行消减筛选噬菌体肽文库。通过共聚焦免疫荧光技术鉴定阳性肽,并在人结肠癌细胞和活检标本中确认其结合能力。通过 BLAST 算法和 MimoDB 数据库对序列进行同源性和现有模拟表位的进一步分析。

结果

鉴定出一种名为 CBP-DWS 的肽,它能够结合一系列人结肠癌细胞系和组织,与正常的人肠道上皮细胞系 NCM460 和正常周围结肠组织几乎没有结合。生物信息学分析表明,CBP-DWS 靶向人类 Glypican-3,它可能参与多种癌症类型的重要细胞功能。

结论

这些研究表明,所选的肽 CBP-DWS 可能是一种新型的结肠癌成像探针候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b044/5765222/4c7aafb781d8/bjc2017366f1.jpg

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