Abstract
Introduction: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are rare pediatric malignancies with a current 5-year overall survival rate of 75% and 50%, respectively. In both tumors, α-fetoprotein (AFP) serves as a clinical tumor marker. To improve the outcome in patients who cannot be cured with chemotherapy and surgery, other treatment options must be tested. However, an animal model for intrahepatic HB is lacking. Aim: To establish an animal model for human HB in NMRInu/nu mice as a first step for a novel orthotopic model using well-characterized AFP-producing HB cell lines. Methods: The human HB cell lines HepT 1, HepT3, and HuH6, and the HCC line HepG2 were tested for their AFP expression. The AFP secreting cell lines were injected subcutaneously in the left flank of 6 week old NMRInu/nu mice. Serum AFP was measured as a parameter for HB growth. Results: HepTl, HuH6 and HepG2 secreted measurable amounts of AFP, thus were used for tumor cell injection. Subcutaneous tumor growth occurred in 70% (HuH6 (HB)) and 50% (HepG2 (HCC)) of the mice after 3.5 and 4.5 weeks, respectively. Mice injected with HepTl (HB) did not yield subcutaneous tumour growth. Serum AFP was highly elevated in HepG2- and HuH6-treated mice if tumor growth occurred, and tumor growth rate was faster for HuH6 than for HepG2. Conclusions: We established an efficient subcutaneous mouse model for human HB. Tumor growth is detected and monitored by serum AFP, and the histological characteristics of the tumor types are preserved. Therefore, this model seems promising both with respect to establishing an animal model for orthotopic human HB and with respect to characterizing and testing alternative treatment strategies in HB in a more physiologic environment.
Published Version
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