Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-17665-8
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Funding
- National Heart, Lung, and Blood Institute (NHLBI) [R01HL134510]
- Macy Easom Cancer Research Foundation
- Texas Hepatocellular Carcinoma Consortium (THCC) CPRIT grant [RP150587]
- Diane Helis Henry and Adrienne Helis Malvin Medical Research Foundation
- NIH [P30CA125123, P30DK56338]
- Texas Children's Department of Surgery Seed Award
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Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human alpha-fetoprotein (AFP) were monitored in the serum of animals. Immunohistochemical and gene expression analyses were also completed on xenograft tumor samples. BLI signal indicative of tumor growth was seen in 55% of HepG2- and Huh-6-injected animals after a period of four to seven weeks. Increased AFP levels correlated with tumor growth. MRI showed large intrahepatic tumors with active neovascularization. HepG2 and Huh-6 xenografts showed expression of beta-catenin, AFP, and Glypican-3 (GPC3). HepG2 samples displayed a consistent gene expression profile most similarto human HB tumors. Intrahepatic injection of HB cell lines leads to liver tumors in mice with growth patterns and biologic, histologic, and genetic features similarto human HB tumors. This orthotopic xenograft mouse model will enable clinically relevant testing of novel agents for HB.
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