title: A Novel Peptide for Simultaneously Enhanced Treatment of Head and Neck Cancer and Mitigation of Oral Mucositis.
abstract: We have characterized a novel 21 amino acid-peptide derived from Antrum Mucosal Protein (AMP)-18 that mediates growth promotion of cultured normal epithelial cells and mitigates radiation-induced oral mucositis in animal models, while suppressing in vitro function of cancer cells. The objective of this study was to evaluate these dual potential therapeutic effects of AMP peptide in a clinically relevant animal model of head and neck cancer (HNC) by simultaneously assessing its effect on tumor growth and radiation-induced oral mucositis in an orthotopic model of HNC. Bioluminescent SCC-25 HNC cells were injected into the anterior tongue and tumors that formed were then subjected to focal radiation treatment. Tumor size was assessed using an in vivo imaging system, and the extent of oral mucositis was compared between animals treated with AMP peptide or vehicle (controls). Synergism between AMP peptide and radiation therapy was suggested by the finding that tumors in the AMP peptide/radiation therapy cohort demonstrated inhibited growth vs. radiation therapy-only treated tumors, while AMP peptide-treatment delayed the onset and reduced the severity of radiation therapy-induced oral mucositis. A differential effect on apoptosis appears to be one mechanism by which AMP-18 can stimulate growth and repair of injured mucosal epithelial cells while inhibiting proliferation of HNC cells. RNA microarray analysis identified pathways that are differentially targeted by AMP-18 in HNC vs. nontransformed cells. These observations confirm the notion that normal cells and tumor cells may respond differently to common biological stimuli, and that leveraging this finding in the case of AMP-18 may provide a clinically relevant opportunity.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: Peili
authors.initials: P
authors.lastname: Chen
authors.affiliation: Biomodels, LLC, Watertown, Massachusetts, 02472, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Biomodels, LLC, Watertown, Massachusetts, 02472, United States of America.|Brigham and Women's Hospital, Boston, Massachusetts, 02115, United States of America.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Sonis
authors.affiliation: Biomodels, LLC, Watertown, Massachusetts, 02472, United States of America.|Mathematics Department, Universidad de Oviedo, Asturias, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Martinez
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, 60637, United States of America.
authors.forename: F Gary
authors.initials: FG
authors.lastname: Toback
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D036361:Peptide Hormones / Q000737:chemistry*; D011878:Radiotherapy / Q000009:adverse effects; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology; D023041:Xenograft Model Antitumor Assays
chemical_list: C477000:GKN1 protein, human; D010446:Peptide Fragments; D036361:Peptide Hormones