Abstract
To clarify the pathogenesis of hepatocellular carcinoma (HCC) and investigate the effects of potential therapies, a number of mouse models have been developed. Subcutaneous xenograft models are widely used in the past decades. Yet, with the advent of in vivo imaging technology, investigators are more and more concerned with the orthotopic models nowadays. Genetically engineered mouse models (GEM) have greatly facilitated studies of gene function in HCC development. Recently, GEM of miR-122 and miR-221 provided new approaches for better understanding of the in vivo functions of microRNA in hepatocarcinogenesis. Chemically induced liver tumors in animals share many of the morphological, histogenic, and biochemical features of human HCC. Yet, the complicated and obscure genomic alternation restricts their applications. In this review, we highlight both the frequently used mouse models and some emerging ones with emphasis on their merits or defects, and give advises for investigators to chose a "best-fit" animal model in HCC research.
Highlights
Liver cancer is the fifth common malignancy and the second leading cause of cancer-related mortalities in the world [1]
Unlike the incidence of lung cancer, which can be reduced by limiting exposure to tobacco smoke, there are many risk factors related with liver cancer, including virus infection [3], chemical carcinogens exposure [4], alcohol abuse [5], or food contaminated with Aspergillus flavus fungus [6]
The results showed that Hsp70 and cytokine-induced killer (CIK) cells worked synergistically and had a significant inhibitory effect against the growth of hepatocellular carcinoma (HCC) xenografts derived from all the 10 patients [16]
Summary
Liver cancer is the fifth common malignancy and the second leading cause of cancer-related mortalities in the world [1]. Other factors, such as the high requirements on instruments and lack of financial support, limit the applications of some costly mouse models Owing to these facts, a knowledgeable selection should be made according to the specific situation investigators come across in their liver cancer researches. Characterized by the short modeling period, the relatively lower cost and the suitability in the evaluation of various methods to treat HCC, implantation models, which can be established either by direct implant of tumor tissue fragments or by inoculation of HCC cell lines in recipient mice, have become the most widely used mouse models in current HCC researches [7,8,9,10,11,12]. Being more to access and manipulate, subcutaneous xenograft model established by HCC cell lines are preferred by researches compared with by human tumor tissue fragments. Spontaneous metastasis rarely occurs when HCC cells are subcutaneously implanted, they do metastasize when they are orthotopically implanted [18]
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