Liver stem cells and hepatocellular carcinoma

Authors

  • Lopa Mishra,

    Corresponding author
    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    2. DVAMC, Washington, DC
    • Department of Surgery, Director, Cancer Genetics, Lombardi Comprehensive Cancer Center, Georgetown University, 3900 Reservoir Road, NW, Medical/Dental Building NW212, Washington, DC 20007
    Search for more papers by this author
    • fax: 202-687-0992

  • Tanuj Banker,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Joseph Murray,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Stephen Byers,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Arun Thenappan,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Aiwu Ruth He,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Kirti Shetty,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • Lynt Johnson,

    1. Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Department of Surgery, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC
    Search for more papers by this author
  • E. P. Reddy

    1. Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA
    Search for more papers by this author

  • Potential conflict of interest: Nothing to report.

Abstract

Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-β), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-β signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC. (HEPATOLOGY 2009;49:318–329.)

Ancillary