A research team at Georgetown Lombardi Comprehensive Cancer Center has described the steps that allow cancer investigators to track, in real time, cancer cells invasion in transparent zebrafish embryos.
Using these fish models, researchers can find answers to cancer questions in one to three days instead of months for the typical mouse model.
Because of this rapidity and the ability to image cancer movement in blood, investigators say the use of zebrafish embryos represent a significant advance in the understanding of cancer biology and experimental drug testing, and may, one day, lead to tumor assessment and treatment evaluation in patients.
The method and its implications are published in the Journal of Visualized Experiments.
Invasion of the blood system is a significant step towards the metastatic spread of cancer cells, which is a significant threat to patients with cancer.
The current method uses human cancer cells in zebrafish and can reveal distinct invasive properties of cancer cells, help identify genes that drive vascular invasion as well as allow to test drugs that inhibit it.
Zebrafish — a tropical freshwater minnow commonly used in aquariums — has been widely used as a model organism in scientific research. But only recently, it has been adapted for use in studying cancer.
The video shows how fluorescent human cancer cells can be injected into developing embryos, and how 24-96 hours later, the ability of the cells to invade the blood and spread can be seen using fluorescence microscopy.
The team tested 7 different breast cancer cell lines to determine which invaded the blood system, and how aggressively.
Using the zebrafish model to uncover drivers of tumor aggression, the team has published two major studies in Oncogene.
One study, published in 2015, demonstrated that the ability of cancer cells to invade is influenced by the density at which those cells are grown.
Another 2016 article, used a screening approach to identify unstudied genes that control cancer cell invasion and metastasis.
Researchers found that keratin-associated protein 5-5 (Krtap5-5) is important for cancer cell invasion out of blood vessels.
Citation: Berens, E. B., Sharif, G. M., Wellstein, A., Glasgow, E. (2016).Testing the Vascular Invasive Ability of Cancer Cells in Zebrafish (Danio Rerio). J. Vis. Exp. (117), e55007. DOI:10.3791/55007.
Figure legend: This Knowridge.com image is credited to Berens, E. B. et al.