title: A novel peptide specifically binding to interleukin-6 receptor (gp80) inhibits angiogenesis and tumor growth.
abstract: Experimental and clinical findings support the essential role of interleukin (IL)-6 in the pathogenesis of various human cancers and provide a rationale for targeted therapeutic investigations. A novel peptide, S7, which selectively binds to IL-6 receptor (IL-6R) alpha chain (gp80) and broadly inhibits IL-6-mediated events, was identified using phage display library screening. The synthetic S7 peptide specifically bound to soluble IL-6R as well as cognate human IL-6R alpha, resulting in a dose-dependent blockade of the interaction between IL-6 and IL-6R alpha. S7 peptide prevents IL-6-mediated survival signaling and sensitizes cervical cancer cells to chemotherapeutic compounds in vitro. The in vitro analysis of antiangiogenic activity showed that S7 peptide substantially inhibits IL-6-induced vascular endothelial growth factor-A expression and angiogenesis in different cancer cell lines. Furthermore, S7 peptide was bioavailable in vivo, leading to a significant suppression of IL-6-induced vascular endothelial growth factor-mediated cervical tumor growth in severe combined immunodeficient mice. These observations show the feasibility of targeting IL-6/IL-6R interaction using the small peptide and highlight its potential in the clinical applications.
authors.affiliation: Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Kuo-Pao
authors.initials: KP
authors.lastname: Lai
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Chiao-Chia
authors.initials: CC
authors.lastname: Chang
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Chi-Lun
authors.initials: CL
authors.lastname: Hu
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Lin-Hung
authors.initials: LH
authors.lastname: Wei
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D019151:Peptide Library; D011485:Protein Binding; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D000093242:Interleukin-6 Inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D015850:Interleukin-6; D009842:Oligopeptides; D019151:Peptide Library; D019947:Receptors, Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D000093242:Interleukin-6 Inhibitors; C467484:VEGFA protein, human