title: Epithelial cell adhesion molecule-positive human hepatic neoplastic cells: development of combined hepatocellular-cholangiocarcinoma in mice.
abstract: OBJECTIVE
  Human combined hepatocellular-cholangiocarcinoma (CHC) expresses several hepatic stem/progenitor cell (HSPC) markers, suggesting this neoplasm originates from HSPCs. We examined the significance of HSPC marker in CHC using a human CHC cell line.
  
  
  METHODS
  We used a human CHC cell line (KMCH-1) previously established in our laboratory. The original tumor was classified as CHC, showing areas of typical hepatocellular carcinoma (HCC) and cholangiocarcinoma (ChC). We examined the expression of HSPC markers and hepatocyte markers in KMCH-1 by flow cytometry (FCM) and quantitative real-time polymerase chain reaction. EpCAM(+) and EpCAM(-) KMCH-1 cells were isolated. Subsequently, their morphological features, HSPC marker expression, and biological characteristics were examined in vitro and in vivo.
  
  
  RESULTS
  FCM showed expression of EpCAM, K7, K19, and ABCG2 in KMCH-1, with various degrees. EpCAM(+) cells expressed K19 mRNA, but did not express α-fetoprotein (AFP). In contrast, EpCAM(-) cells expressed AFP mRNA, but did not express K19. EpCAM(+) cells produced both EpCAM(+) and EpCAM(-) cells, but EpCAM(-) cells produced only EpCAM(-) cells in vitro. EpCAM(+) cells showed higher tumorigenicity and formed larger tumors than EpCAM(-) cells. Inoculation of EpCAM(+) and EpCAM(-) cells produced both ChC and HCC-like component and HCC-like component only, respectively.
  
  
  CONCLUSIONS
  It is speculated that some CHCs may originate from EpCAM(+) neoplastic cells, and that these cells may affect malignant behavior and progression in such CHCs.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018248:Adenoma, Liver Cell / Q000235:genetics* / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009363:Neoplasm Proteins
keywords: combined hepatocellular-cholangiocarcinoma; epithelial cell adhesion molecule; hepatic stem/progenitor cell