title: Dlk-1, a cell surface antigen on foetal hepatic stem/progenitor cells, is expressed in hepatocellular, colon, pancreas and breast carcinomas at a high frequency.
abstract: Delta-like 1 protein (Dlk-1), also known as preadipocyte factor 1 (Pref-1), is a transmembrane and secreted protein with epidermal growth factor (EGF)-like repeats. Dlk-1 is known to be expressed in foetal liver, but absent in neonatal and adult liver in mice and rats. Dlk-1 is also expressed in a subpopulation of hepatic oval cells, which are considered as stem/progenitor cells in rat adult liver. In this study, we generated monoclonal antibodies against human Dlk-1 (hDlk-1) and investigated hDlk-1 expression in human liver and hepatocellular carcinoma (HCC). Like rodent livers, hDlk-1 was detected in foetal liver, but not in adult liver. In HCC, hDlk-1 was positive for 20.5% of the cases examined and was localized in both cytoplasm and cell membrane, whereas hDlk-1 was undetected in viral hepatitis, nodular cirrhosis. Interestingly, hDlk-1 positive HCC was found more frequently in younger patients and its expression was correlated with alpha-fetoprotein expression. Furthermore, hDlk-1 was also detected frequently in colon adenocarcinomas (58%), pancreatic islet carcinoma (50%), and small cell lung carcinoma (50%). Thus, hDlk-1 is a cell surface protein expressed in many carcinomas including HCC and may be a potential target for monoclonal antibody therapy for carcinomas.
authors.affiliation: LivTech Inc., Teikyo University Biotechnology Research Centre 1F, 907 Nogawa, Miyamae, Kawasaki, Kanagawa 216-0001, Japan. yanai@livtech.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanai
authors.forename: Koji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Hijioka
authors.forename: Akira
authors.initials: A
authors.lastname: Kamei
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ikari
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus / Q000166:cytology*; D005434:Flow Cytometry; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins