Subcutaneous and intrahepatic growth of human hepatoblastoma in immunodeficient mice

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• 作者：J. Marco Schnater ; Elisabeth Bruder ; Sibylle Bertschin ; Thomas Woodtli ; Chiel de Theije ; Torsten Pietsch ; Daniel C. Aronson ; Dietrich von Schweinitz ; Wouter H. Lamers and Eleonore S. Kö ; hler
• 刊名：Journal of Hepatology
• 出版年：2006
• 出版时间：September 2006
• 年：2006
• 卷：45
• 期：3
• 页码：377-386
• 全文大小：1370 K

文摘

Background/Aims

Hepatoblastoma is the most frequent malignant pediatric liver tumor. Approximately 25 % of hepatoblastoma patients cannot be cured with current treatment protocols. Additional treatment options must, therefore, be developed. Subcutaneous animal models for hepatoblastoma exist, but a more physiologic intrahepatic model is lacking.

Methods

The α-fetoprotein-expressing hepatoblastoma-cell lines HepT1, HuH6 and the childhood hepatocellular carcinoma-cell line HepG2 were injected subcutaneously and intrasplenically into NMRI nu/nu mice. Tumor growth was monitored by measuring tumor size for subcutaneous and serum human α-fetoprotein levels for intra-abdominal tumors. Tumors were characterized microscopically.

Results

Subcutaneous tumor growth occurred in 70 % (7/10) of mice injected with HuH6 and 50 % (5/10) of mice injected with HepG2. HepT1 did not form tumors. Accumulation of serum α-fetoprotein reflected tumor growth. Intrasplenic growth was seen in 50 % (14/27, HuH6) and 10 % (3/10, HepG2) of the mice, with only HuH6 forming intrahepatic tumors in 25 % (7/27) of the mice. Growth pattern and α-fetoprotein production were similar at the subcutaneous and intra-abdominal location. Intrahepatic grafting occurred by metastatic spread from the spleen, produced well-defined nodules, and was accompanied by a weakened expression of the hepatocyte marker carbamoylphosphate synthetase, and the canalicular markers CD10 and cytokeratin7. The expression of cytokeratin18 and -19, active caspase3, and β-catenin was increased. There were no lung metastases.

Conclusions

We established an intrahepatic mouse model for human hepatoblastoma, in which tumor growth could be monitored by serum α-fetoprotein levels. Engrafting in the liver occurred by metastatic spread from the spleen and was accompanied by some loss of differentiation features.