title: L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Intrahepatic cholangiocarcinoma (ICC), a highly malignant hepatobiliary cancer, has a poor prognosis and is refractory to conventional therapies. The aim of this study is to discover a novel molecular target for the treatment of ICC.
  
  
  METHODS
  To discover novel cancer-associated membrane antigens expressed in ICC cells, we generated monoclonal antibodies (mAb) by immunizing mice with intact ICC cell lines and screened for those that bind to the plasma membrane of ICC cells but not to normal cells. The mAb A10-A3 was selected and its target antigen was identified as the L1 cell adhesion molecule. Expression of L1 in ICC was evaluated by immunohistochemical analysis of tumor samples from 42 ICC patients. The functional significance of L1 expression in the tumor progression of ICC was investigated by L1 suppression, L1 overexpression, and antibody treatment.
  
  
  RESULTS
  L1 was not expressed in normal hepatocytes and intrahepatic bile duct epithelium but highly expressed in 40.5% of ICC patients, remarkably at the invasive front of the tumors. Suppression of L1 with short hairpin RNA significantly decreased proliferation, migration, and invasion of ICC cells in vitro. Consistently, L1 overexpression in ICC cells enhanced proliferation, migration, invasion, and apoptosis resistance. In addition, L1 short hairpin RNA or anti-L1 mAb significantly reduced the tumor growth in nude mice bearing ICC xenograft.
  
  
  CONCLUSIONS
  We identified that L1 is expressed in ICC. L1 plays an important role in the tumor progression of ICC by enhancing cell proliferation, migration, invasion, and survival. L1 may represent a novel therapeutic target for ICC.
authors.affiliation: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungnam National University School of Medicine, Daejon, Korea.
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Shengjin
authors.initials: S
authors.lastname: Li
authors.forename: Jung Whoi
authors.initials: JW
authors.lastname: Lee
authors.forename: Hyunho
authors.initials: H
authors.lastname: Yoon
authors.forename: Chun Jeih
authors.initials: CJ
authors.lastname: Ryu
authors.forename: Soung Hoo
authors.initials: SH
authors.lastname: Jeon
authors.forename: Jae-Hyek
authors.initials: JH
authors.lastname: Lee
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hee Kwan
authors.initials: HK
authors.lastname: Yoon
authors.forename: Young Kwan
authors.initials: YK
authors.lastname: Lee
authors.forename: Bong-Hui
authors.initials: BH
authors.lastname: Kim
authors.forename: Yeon Sung
authors.initials: YS
authors.lastname: Son
authors.forename: Hong Seo
authors.initials: HS
authors.lastname: Choi
authors.forename: Nam-Kyu
authors.initials: NK
authors.lastname: Lim
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Hong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000937:Antigen-Antibody Reactions; D017209:Apoptosis / Q000276:immunology; D001650:Bile Duct Neoplasms / Q000276:immunology* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000276:immunology* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D039842:Neural Cell Adhesion Molecule L1