Premium
Epithelial cell adhesion molecule‐positive human hepatic neoplastic cells: development of combined hepatocellular‐cholangiocarcinoma in mice
Author(s) -
Ogasawara Sachiko,
Akiba Jun,
Nakayama Masamichi,
Nakashima Osamu,
Torimura Takuji,
Yano Hirohisa
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12692
Subject(s) - epithelial cell adhesion molecule , progenitor cell , flow cytometry , hepatocellular carcinoma , cell culture , cancer research , cell adhesion molecule , microbiology and biotechnology , biology , stem cell , immunology , genetics
Background and Aim Human combined hepatocellular‐cholangiocarcinoma ( CHC ) expresses several hepatic stem/progenitor cell ( HSPC ) markers, suggesting this neoplasm originates from HSPC s. 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 , K 7, K 19, and ABCG 2 in KMCH ‐1, with various degrees. EpCAM (+) cells expressed K 19 mRNA , but did not express α‐fetoprotein ( AFP ). In contrast, EpCAM (−) cells expressed AFP mRNA , but did not express K 19. 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 CHC s may originate from EpCAM (+) neoplastic cells, and that these cells may affect malignant behavior and progression in such CHC s.