Epithelial cell adhesion molecule-positive human hepatic neoplastic cells: development of combined hepatocellular-cholangiocarcinoma in mice.
BACKGROUND AND AIM
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.


CONCLUSION
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.
['Ogasawara|Sachiko|S|', 'Akiba|Jun|J|', 'Nakayama|Masamichi|M|', 'Nakashima|Osamu|O|', 'Torimura|Takuji|T|', 'Yano|Hirohisa|H|']
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 D018528:ATP-Binding Cassette Transporters D018248:Adenoma, Liver Cell D000951:Antigens, Neoplasm D001650:Bile Duct Neoplasms D015815:Cell Adhesion Molecules D045744:Cell Line, Tumor D018281:Cholangiocarcinoma D018450:Disease Progression D000071858:Epithelial Cell Adhesion Molecule D015870:Gene Expression D006801:Humans D008113:Liver Neoplasms D009363:Neoplasm Proteins D009378:Neoplasms, Multiple Primary
combined hepatocellular-cholangiocarcinoma hepatic stem/progenitor cell epithelial cell adhesion molecule