Identification of local and circulating cancer stem cells in human liver cancer

Authors

  • Zhen Fan Yang,

    Corresponding author
    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
    • Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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    • These authors contributed equally to this work.

  • Patricia Ngai,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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    • These authors contributed equally to this work.

  • David W. Ho,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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    • These authors contributed equally to this work.

  • Wan Ching Yu,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Michael N.P. Ng,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Chi Keung Lau,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Mandy L. Y. Li,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Ka Ho Tam,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Chi Tat Lam,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Ronnie T. P. Poon,

    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
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  • Sheung Tat Fan

    Corresponding author
    1. Center for Cancer Research and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
    • Department of Surgery, University of Hong Kong Medical Center, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
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    • fax: (852)-28184407.


  • Potential conflict of interest: Nothing to report.

Abstract

Increasing evidence has revealed the importance of cancer stem cells (CSCs) in carcinogenesis. Although liver CSCs have been identified in hepatocellular carcinoma (HCC) cell lines, no data have shown the presence of these cells in human settings. The present study was designed to delineate CSCs serially from HCC cell lines, human liver cancer specimens to blood samples, using CD90 as a potential marker. The number of CD90+ cells increased with the tumorigenicity of HCC cell lines. CD45CD90+ cells were detected in all the tumor specimens, but not in the normal, cirrhotic, and parallel nontumorous livers. In addition, CD45CD90+ cells were detectable in 90% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis. A significant positive correlation between the number of CD45CD90+ cells in the tumor tissues and the number of CD45CD90+ cells in the blood samples was identified. CD90+ cells sorted from cell lines and CD45CD90+ cells from the tumor tissues and blood samples of liver cancer patients generated tumor nodules in immunodeficient mice. Serial transplantation of CD90+ cells from tumor xenografts generated tumor nodules in a second and subsequently third batch of immunodeficient mice. Treatment of CD90+ CSCs with anti-human CD44 antibody induced cell apoptosis in a dose-dependent manner. Conclusion: Identification of CD45CD90+ CSCs in both tumor tissues and circulation suggests that CD45CD90+ could be used as a marker for human liver cancer and as a target for the diagnosis and therapy of this malignancy. (HEPATOLOGY 2008.)

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