title: COP35, a cholangiocarcinoma-binding oligopeptide, interacts with the clathrin heavy chain accompanied by GRP78.
abstract: Cholangiocarcinoma (CCA) is a common carcinoma of the liver, and the majority of patients with CCA have a poor prognosis due to the lack of effective nonsurgical therapies in addition to its rapid progression and inoperability at the time of diagnosis. The development of novel nonsurgical therapeutics that efficiently target CCA could significantly improve the prognosis for patients presenting with CCA. Here, we describe the iterative production and characterization of a novel peptide, designated COP35 (CCA-binding oligopeptide 35), which binds selectively to human CCA, identified by bacteriophage biopanning using the intrahepatic CCA cell line RBE and the normal cholangiocyte cell line MMNK-1. COP35 was found to augment the growth inhibitory effects of 5-fluorouracil (5-FU) against RBE cells. Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA.
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Nagano, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Kitahara
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Alan L
authors.initials: AL
authors.lastname: Parker
authors.forename: Fukuto
authors.initials: F
authors.lastname: Maruta
authors.forename: Naoki
authors.initials: N
authors.lastname: Kubo
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akita
authors.forename: Shiro
authors.initials: S
authors.lastname: Miwa
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism*; D033922:Clathrin Heavy Chains / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D019151:Peptide Library
chemical_list: D000970:Antineoplastic Agents; C561877:CCA-binding oligopeptide 35; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D009842:Oligopeptides; D019151:Peptide Library; D033922:Clathrin Heavy Chains; D005472:Fluorouracil