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  • Review Article
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Hepatocellular carcinoma: insight from animal models

Nature Reviews Gastroenterology & Hepatology volume 9, pages 32–43 (2012)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) ranks as the third most common cause of death from cancer worldwide. Although major risk factors for the development of HCC have been defined, many aspects of the evolution of hepatocellular carcinogenesis and metastasis are still unknown. Suitable animal models are, therefore, essential to promote our understanding of the molecular, cellular and pathophysiological mechanisms of HCC and for the development of new therapeutic strategies. This Review provides an overview of animal models that are relevant to HCC development, metastasis and treatment. For HCC development, this Review focuses on transgenic mouse models of HBV and HCV infection, which provide experimental evidence that viral genes could initiate or promote liver carcinogenesis. Animal models of HCC metastasis provide platforms to elucidate the mechanisms of HCC metastasis, to study the interaction between the microenvironment and HCC invasion and to conduct intervention studies. In addition, animal models have been developed to investigate the effects of new treatment modalities. The criteria for establishing ideal HCC animal models are also discussed.

Key Points

  • Suitable animal models are necessary to provide information on the molecular, cellular and pathophysiological mechanisms of hepatocellular carcinoma (HCC)

  • Transgenic mouse models have provided reliable experimental evidence suggesting that viral hepatitis genes could have a primary role in initiating or promoting liver carcinogenesis

  • Nonviral factors, including oncogenes and environmental carcinogens, might only have a secondary role in liver carcinogenesis, but they could considerably accelerate the transformation of hepatocytes

  • An animal model of metastatic human HCC that incorporates the effects of variation in metastatic potential would provide a unique tool for the study of HCC metastasis

  • Animal models of HCC could be useful for developing and testing novel therapeutic modalities

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Figure 1: Model of liver carcinogenesis based on evidence obtained from transgenic mice.
Figure 2: Theoretical basis for, and description of, a mouse model of HCC incorporating a variation in the propensity for lung metastasis.

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Acknowledgements

The authors receive funding from the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (No. 20921062), and the Fundamental Research Funds for the Central Universities of Ministry of Education of China (No. 4103005; both to Y. Li).

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Authors and Affiliations

  1. Department of Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, China

    Yan Li & Jin-Xuan Hou

  2.  Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, China, 136 Yi Xue Yuan Road, Shanghai, 200032, China

    Zhao-You Tang

Authors
  1. Yan Li
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  2. Zhao-You Tang
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  3. Jin-Xuan Hou
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Contributions

Y. Li, Z.-Y. Tang and J.-X. Hou jointly researched data for the article, wrote the manuscript, and made substantial contributions to discussions of the content. In addition, Z.-Y. Tang reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Zhao-You Tang.

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The authors declare no competing financial interests.

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Li, Y., Tang, ZY. & Hou, JX. Hepatocellular carcinoma: insight from animal models. Nat Rev Gastroenterol Hepatol 9, 32–43 (2012). https://doi.org/10.1038/nrgastro.2011.196

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