Identification of oligopeptides binding to peritoneal tumors of gastric cancer
| Autor: | Jun Nakayama, Leonard W. Seymour, David J. Kerr, Naoto Oku, Noriyuki Akita, Fukuto Maruta, Tomohiro Asai, Shinichi Miyagawa, Alan L. Parker |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Phage display medicine.medical_treatment Amino Acid Motifs Molecular Sequence Data Intraperitoneal injection Biopanning Mice Peptide Library Stomach Neoplasms Consensus Sequence medicine Animals Humans Amino Acid Sequence Peptide library Stomach cancer Peptide sequence Peritoneal Neoplasms Mice Inbred BALB C Antibiotics Antineoplastic business.industry Ascites Cancer General Medicine medicine.disease Oncology Doxorubicin Liposomes Cancer cell Cancer research Female business Cell Adhesion Molecules Oligopeptides |
| Zdroj: | Cancer Science. 97:1075-1081 |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | This is a report of in vivo intraperitoneal biopanning, and we successfully identified a novel peptide to target the multiple peritoneal tumors of gastric cancer. A phage display library was injected directly into the abdominal cavity of mice bearing peritoneal tumors of human gastric cancer, and phages associated with the tumors were subsequently reclaimed from isolated samples. The tumor-associated phages were amplified and the biopanning cycle was repeated five times to enrich for high affinity tumor-selective binding peptides. Finally, a tri-peptide motif, KLP, which showed homology with laminin 5 (a ligand for alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher binding to peritoneal tumors than control phage and were preferentially distributed in tumors rather than in normal organs after intraperitoneal injection into mice. In addition, the KLP phages were more likely to bind to cancer cells in malignant ascites derived from a patient with recurrent gastric cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a strong binding activity to peritoneal tumors without cancer growth effect. Liposomes conjugated with SWKLPPS peptide appeared significantly more often in tumors than control liposomes after intraperitoneal injection into mice. Furthermore, modification of liposomes with SWKLPPS peptide enhanced the antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer. |
| Databáze: | OpenAIRE |
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