Hepatology International

, Volume 11, Issue 2, pp 143–147 | Cite as

Existence of cancer stem cells in hepatocellular carcinoma: myth or reality?

  • Keigo MachidaEmail author
Point of View


The cancer stem cell (CSC) hypothesis has been disproved in many cancers. CSCs may exist in blood cancer, while many epithelial cancers may not have CSCs but tumor-initiating cells (TICs). Several independent studies have provided strong evidence for existence of CSCs in brain, skin, and colon cancers (Mani et al. in Cell 133:704–715, 2008, Joseph et al. in Cancer Cell 13:129–140, 2008, Reya et al. in Nature 414:105–111, 2001), while the CSC hypothesis remains controversial (Magee et al. in Cancer Cell 21:283–296, 2012). Liver TICs have bipotential to give rise to two different lineage types: hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). In the liver cancer field, the origin of HCC and CC is extensively debated. Several groups have validated that TICs gave rise to HCC and CC. Hepatocytes gave rise to HCC. Several groups have demonstrated that oval cells (or liver progenitor cells) give rise to TICs. However, CSCs may be a myth in gastrointestinal cancer, while many groups have validated liver TICs. The definition of CSCs includes pluripotency, while TICs do not have to have pluripotency and only need to have bi- or multipotential to give rise to diverse tumor types and tumor initiation potential in mouse models. The CSC hypothesis therefore controversial (Magee et al. in Cancer Cell 21:283–296, 2012). Cancer tissues contain subpopulations of cells known as tumor-initiating stem-like cells (TICs, so-called CSCs) that have been identified as key drivers of tumor growth and malignant progression with drug resistance. Stem cells proliferate via self-renewing division in which the two daughter cells differ in proliferative potential, with one displaying differentiated phenotype and the other retaining self-renewing activity.


Liver Tumor-initiating stem-like cells (TICs) Cancer stem cells (CSCs) Hepatitis C virus (HCV) Hepatitis B virus (HBV) 



I thank Mr. Peleg Winer at USC for critical reading. This research was supported by NIH grants 1R01AA018857-01, pilot project funding (5P30DK048522-13), P50AA11999 (Animal Core, Morphology Core, and Pilot Project Program), R24AA012885 (Non-Parenchymal Liver Cell Core), the Cell and Tissue Imaging Core of the USC Research Center for Liver Diseases (P30 DK048522), CA123328, and CA108302. This research is also supported by a Research Scholar Grant (RSG MPC122545) and pilot funding (IRG-58-007-48) from the American Cancer Society. Animal imaging was performed by the USC Molecular Imaging Center supported by NIH/NVRR S10.

Compliance with ethical standards

Conflict of interest

The author declares no conflict of interests.


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Copyright information

© Asian Pacific Association for the Study of the Liver 2016

Authors and Affiliations

  1. 1.Southern California Research Center for ALPD and Cirrhosis, Department of Molecular Microbiology and ImmunologyUniversity of Southern California Keck School of MedicineLos AngelesUSA

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