title: Interleukin-4 receptor α-based hybrid peptide effectively induces antitumor activity in head and neck squamous cell carcinoma.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kahori
authors.initials: K
authors.lastname: Seto
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Horibe
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ishige
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamagata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D005887:Gingival Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D015552:Injections, Intralesional; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D010446:Peptide Fragments