Zebrafish Tumor Models

Zebrafish Tumor Models

Cancer is a genetically complex disease that results from the multistep accumulation of somatic, and occasionally inherited, mutations that result in clonal neoplastic cell transformation. Mouse models have provided important insights into these collaborating genetic events that cause cancer formation. Nevertheless, invertebrate models are generally unable to recapitulate the pathogenesis of many human diseases. Due to its small size, rapid maturation time, and heavy brood, the zebrafish has emerged as an important new cancer model. Advances in transgenic and mutagenesis strategies have already resulted in a wide variety of zebrafish cancer models with distinct capabilities for high-throughput screening and in vivo imaging. Besides, the establishment of transgenic lines expressing fluorochromes, such as green fluorescent protein (GFP), in specific developing tissues makes the transparent developing zebrafish particularly conformable to in vivo studies of neoplastic progression, metastasis, and remission.

There are some long-standing methods for establishing a cancer model in zebrafish, including carcinogenic treatment, transgenic regulation, and the transplantation of mammalian tumor cells. By inducing different gene mutations or activating signaling pathways through the use of chemicals, tumors can be induced in multiple organs in zebrafish, such as the liver, pancreas, intestinal canal, muscle, skin, vasculature, and testis. Transgenic technology allows the formation of specific types of tumor by the overexpression of particular oncogenes. All these reverse genetic approaches aim to create a loss-of-function phenotype or they aim to transfer genes found mutated in human cancer patients into the fish. This could also mean generating a zebrafish model with a mutation in an orthologous gene to a human cancer-related phenotype. The xenotransplantation of mammalian tumor cells into zebrafish provides a novel method of studying the interactions between the transplanted tumor cells and the host's vasculature.

Zebrafish models of cancer.

Figure 1. Zebrafish models of cancer. (Hason M, Bartunek P. 2019)

Our Zebrafish Tumor Models

Creative Biogene has established more than 50 genetically engineered zebrafish models of human cancer that closely resemble their human counterparts at the histological and/or genomic levels. Our zebrafish cancer models have accelerated the discovery of new mechanisms driving human cancers and identified new drugs for clinical trials. By using a combination of chemical treatment, genetic technology, and tumor cell xenotransplantation, the vast majority of human tumors can be modeled in zebrafish.

TechnologyTreatmentTypes of induced tumor
Chemical treatmentDimethylbenzanthracene (DMBA)Hepatoma, cholangiocarcinoma and intestinal cancer
Diethylnitrosamine (DEN)Hepatoma, cholangiocarcinoma and pancreatic carcinoma
N-nitrosodimethylamine (NDMA)Hepatoma and cholangiocarcinoma
N-ethyl-N-nitrosourea (ENU)Hepatoma and testicular cancer
N-methyl-N1-nitro-N-nitrosoguanidine (MNNG)Hepatoma and testicular cancer
Genetic technology-knockoutP53Malignant peripheral nerve sheath tumors
APCColon adenoma
NF1Gliomas and malignant peripheral nerve sheath tumors
BRCA2, MYBL2, esp11Testicular cancer
pen/lgl2, bmyb and cds geneEpidermal cancer
GSTT1Lymphoma
vhlHepatoma and intestinal cancer
ptenT-cell acute lymphoblastic leukemia and hemangiosarcoma
Genetic technology-overexpressionMycT-cell leukemia and hepatoma
xmrk and KRASHepatoma
MYCN and fgf8Neuroblastoma
KRASRhabdomyosarcoma
Akt1Lipoma
Scr in p53 mutant backgroundHepatoma
NRAS, BRAF in p53 mutant backgroundMelanoma
EWS-FIL1 in p53 mutant backgroundEwing's sarcoma
XenotransplantationTransplant tumor cells in zebrafishMelanoma, glioma, hepatoma, lung cancer, pancreatic cancer, ovarian carcinomas, breast cancer, prostate cancer, retinoblastoma, leukemia

Advantages

  • Efficiently filter human sequencing data.
  • Directly visualize tumorigenic processes in vivo
  • Large-scale mutagenesis
  • Transgenic models available
  • High-throughput genetic and drug screening

With extensive experience in zebrafish research, our scientists can help you choose the right model and experimental design to achieve your research and development goals.

References

  • Zhao S, et al. A fresh look at zebrafish from the perspective of cancer research. Journal of Experimental & Clinical Cancer Research, 2015, 34(1): 80.
  • Berghmans S, et al. Making waves in cancer research: new models in the zebrafish. Biotechniques, 2005, 39(2): 227-237.
  • Yen J, et al. Zebrafish models of cancer: progress and future challenges. Current opinion in genetics & development, 2014, 24: 38-45.
  • Hason M, Bartunek P. Zebrafish Models of Cancer—New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate. Genes, 2019, 10(11): 935.
  • Astell K R, Sieger D. Zebrafish In Vivo Models of Cancer and Metastasis. Cold Spring Harbor Perspectives in Medicine, 2019: a037077.

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

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