Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) and its advanced form, nonalcoholic steatohepatitis (NASH), is increasing, and as such its contribution to the development of hepatocellular carcinoma is also rising. NAFLD has been shown to influence the immune tumor microenvironment. Therefore, development of pre-clinical mouse models in the context of NAFLD are increasingly important. Here, we describe a mouse model designed to recapitulate the findings of NAFLD followed by rapid induction of orthotopic liver tumors with intrahepatic tumor injection. Additionally, we utilized bioluminescent imaging to monitor tumor growth and response to therapy. The development of one dominant tumor nodule allows precise separation of tumor and liver tissue. This is useful for immunotherapy studies as mononuclear cells from the tumor and the surrounding liver tissue can be analyzed separately.
Highlights
Liver cancer is a common cause of cancer-related death worldwide with approximately 810,000 deaths in 2015 [1]
Non-alcoholic fatty liver disease (NAFLD) and its advanced form, nonalcoholic steatohepatitis (NASH), are recognized as the liver disease associated with metabolic syndrome and characterized by increased fat deposition in the hepatocytes [3,4]
Does NAFLD carry the health risks associated with metabolic syndrome but it increases the risk of developing hepatocellular carcinoma (HCC) which is the most common primary liver cancer in adults [5]
Summary
Liver cancer is a common cause of cancer-related death worldwide with approximately 810,000 deaths in 2015 [1]. Does NAFLD carry the health risks associated with metabolic syndrome but it increases the risk of developing HCC which is the most common primary liver cancer in adults [5]. In order to effectively study the effects of fatty liver disease on immune-based therapies, we designed a model of intrahepatic tumor injection in combination with diets that promote NAFLD. Ol describes a preclinical mouse model of orthotopic HCC development in mice with unde2.rElyxpinergimNenAtaFlLDDesibgyn implantation of syngeneic HCC cell lines which can be monitored by BLI (Figure 1). This model can be used to study treatment strategies and cell biology and immunoloungdye/TrlhiymiisnpmgroNutoAncFooLtl hDdeebsrcyaripibmyespilaanpnrttaehtcileoinnsicoeaftltsmiynongugseoenfemicHodHCeClCoCf wocertlilhtholitnouepsnicwdHheCircClhydcinaevngebloNepmAmoeFnnLittDionr/emdNicbeAywSBiHLthI. To achieve the best results of monitoring tumor growth, we recommend utilizing mice with white fur
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