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

• Published in: Journal of biochemistry (Tokyo) Vol. 148; no. 1; pp. 85 - 92
• Main Authors: Yanai, Hiroyuki, Nakamura, Koji, Hijioka, Susumu, Kamei, Akira, Ikari, Takaaki, Ishikawa, Yuichi, Shinozaki, Eiji, Mizunuma, Nobuyuki, Hatake, Kiyohiko, Miyajima, Atsushi
• Format: Journal Article
• Language: English
• Published: England Japanese Biochemical Society 01.07.2010; Oxford University Press
• Subjects: Adult; Animals; Antibodies, Monoclonal - immunology; Antigens, Neoplasm - analysis; Antigens, Neoplasm - metabolism; Antigens, Surface - metabolism; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line; cell surface protein; colon adenocarcinoma; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Female; Fetus - cytology; Flow Cytometry; hDlk-1; hepatocellular carcinoma (HCC); Hepatocytes - metabolism; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins - metabolism; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Membrane Proteins - metabolism; Mice; Neoplasms - metabolism; Neoplasms - pathology; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Rats; small cell lung carcinoma; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvq034

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.