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 αvβ6 rather than other av-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 αvβ6-dependent manner. Besides, we showed that integrin αvβ6 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.
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