Isolation and characterization of tumorigenic extrahepatic cholangiocarcinoma cells with stem cell-like properties

Authors

  • Min Wang,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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    • Min Wang and Juan Xiao contributed equally to this work.

  • Juan Xiao,

    1. Department of Obstetrics and Gynecology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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    • Min Wang and Juan Xiao contributed equally to this work.

  • Min Shen,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Yu Yahong,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Rui Tian,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Feng Zhu,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Jianxin Jiang,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Zhiyong Du,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Jun Hu,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Wensong Liu,

    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
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  • Renyi Qin

    Corresponding author
    1. Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, People's Republic of China
    • Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan City, Hubei Province, 430030 People's Republic of China
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    • Tel.:+27-8366-3814, Fax: +27-8366-3874


Abstract

Recent studies suggest that the ability to form and grow tumors specifically resides in a small cell population called cancer stem cells (CSCs). These studies were conducted mainly on various human cancers; however, isolation and characterization of stem cells from cholangiocarcinoma have not been attempted. The molecular markers CD24, CD44, CD34, and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of CSCs. In this study, we used these markers to identify a subpopulation of cells in extrahepatic cholangiocarcinoma (ECC) with cancer stem/progenitor cell-like properties. We found that CD24+CD44+EpCAMhigh cells (0.39–2.27%) were present in human ECC tissues. The expression of a CD24+CD44+EpCAMhigh subpopulation was consistent with primary cancers and could be duplicated during serial in vivo passaging in NOD/SCID mice. CD24+CD44+EpCAMhigh cells isolated from 3 cholangiocarcinoma xenografts showed high tumorigenic potential compared with CD24CD44EpCAMlow/− cells. These tumorigenic ECC cells exhibited the stem cell properties of self-renewal and ability to produce heterogeneous progeny. We report the identification of a CSC population in ECC characterized by CD24, CD44 and EpCAM phenotypes. Our findings could provide new insight into the tumorigenesis of cholangiocarcinoma and offer a potential target for anti-cancer therapy.

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