Zebrafish Melanoma Models

Melanoma is the most aggressive and deadly form of skin cancer. Although advances in detection and treatment have reduced the incidence of many cancers, the incidence of melanoma has risen dramatically in recent decades. Therefore, it is important to identify and monitor individuals at genetic risk for melanoma and to better identify premetastatic lesions in these patients. While tremendous efforts have been made to identify the genetic defects that lead to melanoma, there are clearly many more genes involved in the disease.

Identifying the genetic, molecular and cytopathology of melanoma is fundamental to improving our diagnostic tools and developing new treatments. Over the past two decades, the zebrafish has become an established model and an excellent platform for this type of research. Certain properties of zebrafish aid in the study of melanocyte biology and melanoma. Zebrafish melanocytes are externally visible, and individual cells can be seen in live animals. In mammals, melanin-containing melanosomes are transported to adjacent keratinocytes. However, zebrafish melanocytes retain melanin and are therefore a reliable and useful marker of cell types. In addition, a large number of zebrafish pigmentation mutants that affect melanocyte specification, differentiation and function are available, and the defective genes in these mutants are conserved in mammals.

Fig.1 Melanocytic lesions in zebrafish expressing BRAFV600E.

Our Zebrafish Melanoma Models

Creative Biogene has established several zebrafish melanoma models based on years of experience in zebrafish research. In all of these models, there is a region of cancerous cells with the same genetic alterations that require additional genetic or epigenetic changes to eventually form tumors. We tend to develop melanomas on zebrafish embryos by xenotransplantation. During embryogenesis, hundreds of cells can be implanted in the absence of an adaptive immune system. Migration and invasion of engrafted tumor cells (using melanin or GFP as markers) can be easily visualized and quantified at the single-cell level. Our system can thus serve as an attractive tool for chemical or genetic screening to identify novel modifiers of the metastatic melanoma phenotype.

Our zebrafish melanoma models not only provide the ability to study melanoma in a controlled environment, but also provide an opportunity to discover a stable background of novel melanoma modifier genes. Using our zebrafish model as a screening platform, with its high throughput and tumorigenesis as readouts, a small number of driver genes could potentially be identified from the many passenger genes present in patient melanoma sequences. Furthermore, our zebrafish models can provide unique insights into pathogenesis and therapy, facilitating the discovery of new melanoma therapies from existing drug libraries.

Advantages

• Easy observation of tumorigenesis and tumor-induced phenotypes in live animals
• Mass mutagenesis
• High-throughput gene/drug screening
• Time-lapse imaging of development in vitro
• Allow precise measurement of melanocytes at single-cell resolution in live animals

References

1. Ceol CJ, et al. Melanoma biology and the promise of zebrafish. Zebrafish. 2008, 5(4):247-255.
2. Frantz WT, Ceol CJ. From Tank to Treatment: Modeling Melanoma in Zebrafish. Cells. 2020, 9(5):1289.
3. Kaufman CK, et al. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science. 2016, 351(6272):aad2197.

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