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OBJECTIVES: We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging. METHODS: The biopanning technique using phage peptide display libraries was performed on HCC cells in vitro, and a phage clone expressing the HCC-binding peptide motif was selected. The binding activity of the selected phage was evaluated by plaque infection assay and immunofluorescence on cell lines. In addition, the binding activity of the peptide-expressing phage was investigated using HCC specimens derived from patients who had undergone hepatectomy for HCC. RESULTS: A heptapetide, Thr-Thr-Pro-Arg-Asp-Ala-Tyr (TTPRDAY), was identified as a motif binding to HCC. TTPRDAY bound specifically to HCC cells in comparison with other cancer cells, and the binding to HCC cells was also confirmed by immunofluorescence. In addition, the synthesized TTPRDAY peptide showed binding activity and a non-mitogenic effect on HCC cells in vitro. TTPRDAY-presenting phage showed more significant binding to HCC cells derived from specimens obtained from actual patients than to non-cancerous liver tissue. CONCLUSION: The motif TTPRDAY, identified by the biopanning technique, shows significant binding to HCC cells.

Original publication




Journal article



Publication Date





136 - 145


Aged, Carcinoma, Hepatocellular, Cell Proliferation, Humans, Liver Neoplasms, Male, Middle Aged, Mutagenicity Tests, Oligopeptides, Peptide Library, Salmonella typhimurium, Tumor Cells, Cultured