Zebrafish Pancreatic Cancer Models

Pancreatic cancer is one of the most aggressive malignancies worldwide, with a very low survival rate after diagnosis. KRAS mutation is an early event in pancreatic tumorigenesis and is critical for cancer initiation and progression. Elucidating the underlying mechanisms regulating pancreatic organogenesis may help to identify molecular pathways underlying exocrine pancreatic carcinogenesis. The great progress in mouse models of pancreatic cancer has raised expectations, however, the results of preclinical trials of most new drugs that have shown good efficacy against invasive pancreatic ductal adenocarcinoma in mouse models have not been confirmed in the clinical stage. Addressing this fundamental problem may require the development of new animal models.

The zebrafish is an amenable vertebrate model for genetic manipulation, and its pancreas shares many similarities with the human pancreas, including similar transcription factors and genetic networks for pancreatic development and function. Therefore, zebrafish is a suitable in vivo model to study pancreatic cancer. Various approaches using forward and reverse genetics, chemical genetics, and transgenes in zebrafish have demonstrated universally conserved regulation of mammalian genes and uncovered novel genetic pathways in exocrine pancreas development. Growing evidence supports the use of zebrafish as a model for human malignant disease, including pancreatic cancer. The study demonstrates that genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets for human pancreatic cancer.

Fig.1 Implantation of two pancreatic cancer cell lines into the same zebrafish embryo.

Our Zebrafish Pancreatic Cancer Models

Creative Biogene has established mature zebrafish pancreatic cancer models that highly recapitulate the development of human pancreatic intraepithelial neoplasia. The histological and immunohistochemical features of experimental tumors in these models closely resemble human pancreatic intraepithelial neoplasia (PanIN). Within the entire abnormal area, the entire differentiation spectrum from PanIN-1 to PanIN-3 can be observed.

Creative Biogene can not only establish transgenic zebrafish expressing oncogenic K-ras, but also provide zebrafish tumor xenograft models. We aim to provide valuable tools for dissecting pancreatic cancer pathogenesis and toxicology, as well as advance your understanding of the genetic regulation of early developmental events in the pancreas. In addition, we are a one-stop shop and our analysis of the zebrafish pancreas will help your understanding of genetic regulation and biological mechanisms during organogenesis. Our zebrafish model promises to provide new insights into how aberrant developmental pathways contribute to pancreatic tumor formation and growth, with the potential to generate potent biomarkers and targets and effective and safe treatments in pancreatic cancer.

Advantages

• Easy observation of tumorigenesis and tumor-induced phenotypes in live animals
• Multiple induction models
• Mass mutagenesis
• High-throughput gene/drug screening

References

1. Marques IJ, et al. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model. BMC Cancer. 2009, 9:128.
2. Park JT, Leach SD. Zebrafish model of KRAS-initiated pancreatic cancer. Anim Cells Syst (Seoul). 2018, 22(6):353-359.
3. Yee NS, Pack M. Zebrafish as a model for pancreatic cancer research. Methods Mol Med. 2005, 103:273-98.

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