Zebrafish Liver Cancer Models

Liver cancer is one of the most common cancers in the world and the second leading cause of cancer death. Most patients with liver cancer are diagnosed at an advanced stage when treatment is not possible. Current medical treatments prolong mean overall survival only for a short period of time. Gene mutations associated with liver cancer vary widely. Therefore, transgenic and mutant animal models are needed to study the molecular effects of specific mutations and to develop targeted therapies.

Zebrafish cancer models are rapidly gaining popularity and yielding clinically translatable insights. The zebrafish model system has several advantages over other animal models. Their high fecundity and low rearing costs allow for extensive genetic screening. Zebrafish are transparent and develop externally, allowing in vivo imaging and analysis of normal organogenesis mechanisms. In addition, small molecule drugs can be added directly to zebrafish water. If a larval stage phenotype is discovered, high-throughput chemical screening of the whole organism can be performed to identify relevant signaling pathways and evaluate potential mechanisms of molecular intervention.

Genes and pathways involved in hepatogenesis and liver cancer are largely conserved between zebrafish and humans. Hepatocytes have similar functions in zebrafish and mammals and display similar origins in shared histopathological features such as steatosis, cholestasis, and tumor formation. Therefore, the study of liver development in zebrafish can provide new insights into the development of liver cancer.

Fig. 1 Induction of liver tumors in TO(Myc) fish.

Our Zebrafish Liver Cancer Models

Creative Biogene establishes zebrafish liver cancer models through transgenic, genome editing technology, xenotransplantation, drug treatment and other methods. We have developed transgenic and mutant zebrafish to mimic various aspects of Wnt and Ras signaling and the epigenetic basis of hepatocellular carcinoma (HCC). Pathological features observed in these transgenic zebrafish models include steatohepatitis, fibrosis chemotherapy, liver cirrhosis and HCC. These models will provide insight into the pathogenesis of liver cancer and associated drug discovery and toxicology, and enable the evaluation of novel small molecule inhibitors.

Advantages

• Easily monitor the progression of the disease
• Multiple induction models
• Mass mutagenesis
• High-throughput gene/drug screening

References

1. Lu JW, et al. Zebrafish as a disease model for studying human hepatocellular carcinoma. World J Gastroenterol. 2015, 21(42):12042-12058.
2. Wrighton PJ, Oderberg IM, Goessling W. There Is Something Fishy About Liver Cancer: Zebrafish Models of Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol. 2019, 8(3):347-363.

For research use only. Not intended for any clinical use.