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Published on: January 22, 2018
Identification of oligopeptides binding to peritoneal tumors of gastric cancer
Noriyuki Akita1, Fukuto Maruta, Leonard W Seymour
1Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Abstract:
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.
Insights
Researchers identified a novel KLP peptide targeting gastric cancer peritoneal tumors. This peptide, delivered via phage or liposomes, shows high tumor affinity and enhances chemotherapy, offering a potential treatment for peritoneal metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Gastric cancer frequently metastasizes to the peritoneum, leading to poor prognosis.
- Effective targeted therapies for peritoneal gastric cancer are limited.
- Identifying specific tumor-targeting ligands is crucial for developing novel treatment strategies.
Purpose of the Study:
- To identify and characterize a novel peptide targeting multiple peritoneal tumors of gastric cancer using in vivo biopanning.
- To evaluate the targeting efficacy and therapeutic potential of the identified peptide and its derivatives in preclinical models.
Main Methods:
- In vivo intraperitoneal biopanning of a phage display library in mice with gastric cancer peritoneal tumors.
- Amplification and selection of tumor-associated phages over five cycles.
- Identification and synthesis of the KLP peptide motif (SWKLPPS).
- Evaluation of peptide and liposome-peptide conjugate targeting in vitro and in vivo.
- Assessment of peptide-modified liposomes in combination with adriamycin for antitumor activity.
Main Results:
- A tri-peptide motif, KLP, was identified as a high-affinity binding peptide for gastric cancer peritoneal tumors.
- KLP-displaying phages showed 64-fold higher tumor binding and preferential tumor distribution compared to control phages.
- The synthesized peptide SWKLPPS demonstrated strong binding to peritoneal tumors and enhanced the antitumor activity of adriamycin when conjugated to liposomes.
- Liposomes conjugated with SWKLPPS showed significantly increased tumor accumulation.
Conclusions:
- The KLP peptide motif is a promising targeting ligand for gastric cancer peritoneal metastasis.
- KLP-based peptide and liposome conjugates offer a potential strategy for targeted drug delivery and enhanced antitumor therapy.
- Further investigation into KLP peptide for clinical application in peritoneal gastric cancer is warranted.
