Mouse Models of Hepatocellular Carcinoma: Classification, Advancement, and Application

Abstract

Hepatocellular carcinoma (HCC) is the subtype of liver cancer with the highest incidence, which is a heterogeneous malignancy with increasing incidence rate and high mortality. For ethical reasons, it is essential to validate medical clinical trials for HCC in animal models before further consideration on humans. Therefore, appropriate models for the study of the pathogenesis of the disease and related treatment methods are necessary. For tumor research, mouse models are the most commonly used and effective in vivo model, which is closer to the real-life environment, and the repeated experiments performed on it are closer to the real situation. Several mouse models of HCC have been developed with different mouse strains, cell lines, tumor sites, and tumor formation methods. In this review, we mainly introduce some mouse HCC models, including induced model, gene-edited model, HCC transplantation model, and other mouse HCC models, and discuss how to choose the appropriate model according to the purpose of the experiments.

Keywords: gene-edited mice; hepatocellular carcinoma; metastasis; mouse model; transplantation model.

Figure 1

The classification, advancement, and application of mouse HCC models. HCC, hepatocellular carcinoma; HBV, hepatitis B virus; NAFLD-NASH, non-alcoholic fatty liver disease-non-alcoholic steatohepatitis.

Figure 2

Three steps used to choose a mouse model. Firstly, the purpose of the experiment should be defined. Studies are usually about generation of HCC, immune microenvironment, or drug effect test. Different animal models are available for different experimental purposes. Secondly, the mouse strain and tumor source should be chosen. Depending on different purposes, gene-edited mice, SCID mice, normal mice, and mouse- or patient-derived tissue, human or mouse cell lines could be chosen. Lastly, researchers should choose the tumor site. Most of the time, the subcutaneous model will be chosen in the initial test, and orthotopic or metastasis model will be used in the final test.