Interleukin-4 receptor α-based hybrid peptide effectively induces antitumor activity in head and neck squamous cell carcinoma

Seto,Kahori; Shoda,Junichi; Horibe,Tomohisa; Warabi,Eiji; Ishige,Kazunori; Yamagata,Kenji; Kohno,Masayuki; Yanagawa,Toru; Bukawa,Hiroki; Kawakami,Koji

doi:10.3892/or.2013.2387

Interleukin-4 receptor α-based hybrid peptide effectively induces antitumor activity in head and neck squamous cell carcinoma

Authors:
- Kahori Seto
- Junichi Shoda
- Tomohisa Horibe
- Eiji Warabi
- Kazunori Ishige
- Kenji Yamagata
- Masayuki Kohno
- Toru Yanagawa
- Hiroki Bukawa
- Koji Kawakami
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Affiliations: Department of Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8575, Japan, Medical Science Section, Faculty of Medicine, University of Tsukuba Graduate School, Ibaraki 305-8575, Japan, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto 606-8501, Japan, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan, Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan, Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan
Published online on: April 4, 2013 https://doi.org/10.3892/or.2013.2387
Pages: 2147-2153

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Abstract

Interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of various human solid tumors including head and neck squamous cell carcinoma (HNSCC). We designed a novel IL-4Rα-lytic hybrid peptide composed of a binding peptide to IL-4Rα and a cell-lytic peptide. In the present study, we evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular-targeted therapy in HNSCC. Immunoblot analysis revealed that IL-4Rα was expressed in all tested HNSCC cell lines (HSC-2, HSC-3, HSC-4, Ca9-22 and OSC-19), but not in a human normal keratinocyte (HaCaT) cell line. Immunohistochemical expression levels of IL-4Rα in HNSCC tissues were higher compared to those in normal epithelial tissue. The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in all five cancer cell lines with a concentration that killed 50% of all cells (IC50) as low as 10 µM. HaCaT cells were less sensitive to this peptide with an IC50 of >30 µM. In addition, intratumoral administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human HNSCC in vivo. These results indicate that the IL-4Rα-lytic hybrid peptide may serve as a potent agent to provide a novel therapy for patients with HNSCC.

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1	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar
2	Seiwert TY and Cohen EE: State-of-the-art management of locally advanced head and neck cancer. Br J Cancer. 92:1341–1348. 2005. View Article : Google Scholar : PubMed/NCBI
3	Forastiere AA, Goepfert H, Maor M, et al: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 349:2091–2098. 2003. View Article : Google Scholar : PubMed/NCBI
4	Dietz A, Boehm A, Mozet C, Wichmann G and Giannis A: Current aspects of targeted therapy in head and neck tumors. Eur Arch Otorhinolaryngol. 265(Suppl 1): S3–S12. 2008. View Article : Google Scholar : PubMed/NCBI
5	Price KA and Cohen EE: Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 13:35–46. 2012. View Article : Google Scholar : PubMed/NCBI
6	Kirby AM, A’Hern RP, D’Ambrosio C, et al: Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer. Br J Cancer. 94:631–636. 2006.PubMed/NCBI
7	Herbst RS, Arquette M, Shin DM, et al: Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 23:5578–5587. 2005. View Article : Google Scholar : PubMed/NCBI
8	Shimamura T, Royal RE, Kioi M, Nakajima A, Husain SR and Puri RK: Interleukin-4 cytotoxin therapy synergizes with gemcitabine in a mouse model of pancreatic ductal adenocarcinoma. Cancer Res. 67:9903–9912. 2007. View Article : Google Scholar : PubMed/NCBI
9	Ishige K, Shoda J, Kawamoto T, et al: Potent in vitro and in vivo antitumor activity of interleukin-4-conjugated Pseudomonas exotoxin against human biliary tract carcinoma. Int J Cancer. 123:2915–2922. 2008. View Article : Google Scholar : PubMed/NCBI
10	Pastan I, Hassan R, Fitzgerald DJ and Kreitman RJ: Immunotoxin therapy of cancer. Nat Rev Cancer. 6:559–565. 2006. View Article : Google Scholar
11	Weber F, Asher A, Bucholz R, et al: Safty, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J Neurooncol. 64:125–137. 2003. View Article : Google Scholar : PubMed/NCBI
12	Attia P, Powell DJ Jr, Maker AV, Kreitman RJ, Pastan I and Rosenberg SA: Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2. J Immunother. 29:208–214. 2006. View Article : Google Scholar : PubMed/NCBI
13	Choudhary S, Mathew M and Verma RS: Therapeutic potential of anticancer immunotoxins. Drug Discov Today. 16:495–503. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kohno M, Horibe T, Haramoto M, et al: A novel hybrid peptide targeting EGFR-expressing cancers. Eur J Cancer. 47:773–783. 2011. View Article : Google Scholar : PubMed/NCBI
15	Garland L, Gitlitz B, Ebbinghaus S, et al: Phase I trial of intravenous IL-4 Pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor. J Immunother. 28:376–381. 2005.PubMed/NCBI
16	Forastiere A, Koch W, Trotti A and Sidransky D: Head and neck cancer. N Engl J Med. 345:1890–1900. 2001. View Article : Google Scholar
17	Goon PK, Stanley MA, Ebmeyer J, et al: HPV & head and neck cancer: a descriptive update. Head Neck Oncol. 1:362009.
18	Bosch F and Rosich L: The contributions of Paul Ehrlich to pharmacology: a tribute on the occasion of the centenary of his Nobel Prize. Pharmacology. 82:171–179. 2008. View Article : Google Scholar : PubMed/NCBI
19	Pastan I, Hassan R, FitzGerald DJ and Kreitman RJ: Immunotoxin treatment of cancer. Annu Rev Med. 221–237. 2007. View Article : Google Scholar
20	Kreitman RJ: Immunotoxins for targeted cancer therapy (review). AAPS J. 8:532–551. 2006. View Article : Google Scholar
21	Li Z, Yu T, Zhao P and Ma J: Immunotoxins and cancer therapy. Cell Mol Immunol. 2:106–112. 2005.PubMed/NCBI
22	Horibe T, Kohno M, Haramoto M, Ohara K and Kawakami K: Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent. J Transl Med. 9:82011. View Article : Google Scholar : PubMed/NCBI
23	Tada N, Horibe T, Haramoto M, Ohara K, Kohno M and Kawakami K: A single replacement of histidine to arginine in EGFR-lytic hybrid peptide demonstrates the improved anticancer activity. Biochem Biophys Res Commun. 407:383–388. 2011. View Article : Google Scholar : PubMed/NCBI
24	Strome SE, Kawakami K, Alejandro D, et al: Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models. Clin Cancer Res. 8:281–286. 2002.PubMed/NCBI
25	Mehrotra R, Varricchio F, Husain SR and Puri RK: Head and neck cancers, but not benign lesions, express interleukin-4 receptors in situ. Oncol Rep. 5:45–48. 1998.PubMed/NCBI
26	Kawakami K, Leland P and Puri RK: Structure, function, and targeting of interleukin 4 receptors on human head and neck cancer cells. Cancer Res. 60:2981–2987. 2000.PubMed/NCBI
27	Mimeault M, Hauke R, Mehta PP and Batra SK: Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med. 11:981–1011. 2007. View Article : Google Scholar : PubMed/NCBI