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Liver Cancer Stem Cells

Stewart Sell, Hyam L. Leffert

From the Wadsworth Center and Ordway Research Institute and University at Albany, Empire State Plaza, Albany, NY; and the School of Medicine, Department of Pharmacology and Center for Molecular Genetics, University of California at San Diego, La Jolla, CA

Corresponding author: Stewart Sell, MD, Wadsworth Center, Empire State Plaza, Room C-551, Albany, NY; 12201; e-mail: ssell{at}wadsworth.org

In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

Supported by UCSD Superfund 5-P42 ES10337, National Institutes of Health Grants No. 1-R01-CA112481 (S.S.), 1-R21-AI067354, and 1-R01-CA113602 (H.L.L.).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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