Abstract
Though the cancer research community has used mouse xenografts for decades more than zebrafish xenografts, zebrafish have much to offer: they are cheap, easy to work with, and the embryonic model is relatively easy to use in high-throughput assays. Zebrafish can be imaged live, allowing us to observe cellular and molecular processes in vivo in real time. Opponents dismiss the zebrafish model due to the evolutionary distance between zebrafish and humans, as compared to mice, but proponents argue for the zebrafish xenograft’s superiority to cell culture systems and its advantages in imaging. This review places the zebrafish xenograft in the context of current views on cancer and gives an overview of how several aspects of this evolutionary disease can be addressed in the zebrafish model. Zebrafish are missing homologs of some human proteins and (of particular interest) several members of the matrix metalloproteinase (MMP) family of proteases, which are known for their importance in tumour biology. This review draws attention to the implicit evolutionary experiment taking place when the molecular ecology of the xenograft host is significantly different than that of the donor.
Highlights
The zebrafish xenograft is a model for tumour biology that has grown in popularity in the last decade, most often used to test drugs for their cytotoxic, anti-metastatic, or anti-angiogenic properties, and as a more sophisticated alternative to 2D culturing assays that use artificial matrix or matrix extract to investigate cellular invasiveness
The zebrafish xenograft is defended for its ability to replicate 2D and 3D culture results as well as, paradoxically, for its supposed superiority to them
Many reviews of the field exist that defend the use of zebrafish as a model for cancer research [4,5,6,7], and similar balanced criticisms exist for mouse models
Summary
The zebrafish xenograft is a model for tumour biology that has grown in popularity in the last decade, most often used to test drugs for their cytotoxic, anti-metastatic, or anti-angiogenic properties, and as a more sophisticated alternative to 2D culturing assays that use artificial matrix or matrix extract to investigate cellular invasiveness. Cancer is a complex evolutionary and ecological disease [8,9,10,11], in that tumour cells are genetically variable, and their interactions with each other and their tissue microenvironment (TME) provides a complex selection landscape. Drug treatment strategies are often applied in the clinic as cocktails to lower the chance of cancer resistance and escape Cancer cells and their microenvironment can be viewed through an ecological, as well as evolutionary, lens. Xenografts may help to ask questions about the principles of the ecology of cancer in the same way that invasive species in a new environment can provide insight into ecological mechanisms that are important in its control [18] The zebrafish xenograft, both despite and because of its evolutionary distance from mammals, can offer insights into the mechanisms associated with cancer progression. Gaining a better understanding of how mechanisms are conserved from species to species will lead to a better frame of reference for how they are conserved from cancer to cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
