Design of a Neonatal Orthotopic Metastatic Xenograft Model of Hepatoblastoma in Mice.

Abstract

Introduction: Hepatoblastoma (HB) is the most frequent liver cancer in children, typically occurring before the age of five. Thanks to the combination of chemotherapy and surgery, the 5-year survival rate following diagnosis is approximately 83%. Today, the main challenge is the efficient treatment of high-risk patients, particularly those presenting with lung metastasis or experiencing relapse. To better study HB and validate new therapeutic options, various animal models have been developed in mice, chick and zebrafish. However, none of these models fully recapitulates the complexity and juvenile context of the disease, as observed in very young patients.

Methods: To account for the young age of patients and better mimic the hepatic microenvironment in which HBs develop, we established an innovative orthotopic xenograft model of HB in juvenile mice, which also generates lung metastases. Eleven-day-old immunocompromised mice were injected intrahepatically with Huh6 cells. Tumor progression was monitored through bioimaging and confirmed post-euthanasia by direct examination of the liver and lungs using microscopic imaging and immunohistochemistry. To further validate the model, some implanted mice were treated with cisplatin, and the response of HB cells to this DNA intercalating agent was assessed.

Conclusion: This neonatal orthotopic xenograft model of HB in mice reproduces lung metastases and exhibits sensitivity to cisplatin. It fully mimics the developmental progression of this pediatric tumor and clearly surpasses existing models in adult mice, paving the way for more robust basic research investigations and preclinical studies in whole animals.