Characterization of inflammatory pseudotumors in a large animal model of liver cancer.

Abstract

BACKGROUND: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail. METHODS: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced in the tissue. The study consisted of 3 animals in 3 cohorts (total of 9 animals) that were evaluated at 14, 21, and 28 days. CT imaging, immunohistochemistry, multiplex immunofluorescence, and comprehensive blood analyses were used to quantify composition of the hepatic masses that developed following AdCre inoculation. RESULTS: The tumors were hypovascular on CT and predominantly composed of CD45+ cells with a strong lymphohistiocytic component, with no carcinomas identified. Ki-67 staining showed proliferation of CD45+ immune cells but no neoplastic component. To provide further insight, the results are evaluated in the context of tumor growth kinetics. CONCLUSION: While progress has been made in generating targetable lesions, achieving a robust large animal model of liver cancer that faithfully recapitulates the human disease remains a challenging goal.