从生物淘选获得的针对 alphavbeta6 的环肽，具有头颈部鳞状细胞癌的临床应用潜力。

Cyclic alphavbeta6-targeting peptide selected from biopanning with clinical potential for head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan.

出版信息

Head Neck. 2010 Feb;32(2):160-72. doi: 10.1002/hed.21166.

DOI:10.1002/hed.21166

PMID:19572290

Abstract

BACKGROUND

A cyclic peptide-displaying phage library was used for biopanning on oral squamous cell carcinoma (OSCC) cells to identify cancer-targeting peptides. This study was designed to characterize the receptor specificity of a candidate phage clone/peptide (phage/peptide-29) and to explore the clinical potential of this peptide.

METHODS

Immunofluorescent confocal microscopy, phage binding assay, and immunohistochemical studies were used to demonstrate the receptor specificity of phage/peptide-29. The effect of peptide-29 on the proliferation of OSCC cells was studied using 3-dimensional (3D) cell cultures.

RESULTS

Phage/peptide-29 preferentially binds integrin alphavbeta6 rather than other alphav-associated integrins. Peptide-29 significantly inhibits the proliferation of OSCC cells in 3D cell cultures. On human pathological sections, phage-29 targets oral cancer cells in a alphavbeta6-dependent manner. Besides, we showed that integrin alphavbeta6 is universally (94.7%, 36/38) expressed in all major kinds of head and neck squamous cell carcinomas (HNSCC).

CONCLUSIONS

Peptide-29 selected from biopanning may have clinical potential for HNSCC.

摘要

背景

采用展示环肽的噬菌体文库对口腔鳞状细胞癌（OSCC）细胞进行生物淘选，以鉴定针对癌症的肽。本研究旨在鉴定候选噬菌体克隆/肽（噬菌体/肽-29）的受体特异性，并探索该肽的临床潜力。

方法

利用免疫荧光共聚焦显微镜、噬菌体结合试验和免疫组化研究，来证明噬菌体/肽-29 的受体特异性。利用三维（3D）细胞培养来研究肽-29 对 OSCC 细胞增殖的影响。

结果

噬菌体/肽-29 优先结合整合素 alphavbeta6，而不是其他 alphav 相关整合素。肽-29 显著抑制 3D 细胞培养中的 OSCC 细胞增殖。在人类病理切片上，噬菌体-29 以 alphavbeta6 依赖性方式靶向口腔癌细胞。此外，我们表明整合素 alphavbeta6 普遍（94.7%，36/38）表达于所有主要类型的头颈部鳞状细胞癌（HNSCC）中。