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Transparent adult zebra fish reveal cancer metastasis

BioPhotonics
Feb 2008
Scientists have used zebra fish embryos with fluorescent labels to study many aspects of biology and disease. The embryos are a useful model organism because they are genetically similar to humans and are transparent. However, after four weeks they reach adulthood and become opaque.

Researchers at Children’s Hospital Boston recently created a zebra fish mutant that is transparent throughout its life. This could allow scientists to observe processes such as tumor metastasis in a living organism as well as to study processes in the fish’s visible organs, which include the brain, heart and digestive tract.

As detailed in the Feb. 7 issue of Cell Stem Cell, the investigators created the transparent fish by mating a zebra fish mutant that lacks reflective pigment with one that lacks black pigment. Normal zebra fish have reflective, black and yellow pigments in their skin; thus, the offspring of the mutants had only yellow pigment and essentially looked clear (see figure). The scientists call this new zebra fish mutant “casper.”

AsWeFish_clear-female-zebrafish.jpg

Courtesy of Richard White, Children’s Hospital Boston.

The reseachers used the clear zebra fish to examine how cancer spreads. They created a fluorescent melanoma tumor in the fish’s abdominal cavity and, within five days, examined the cancer cells spreading. They could see individual cells metastasize and observed that the melanoma cells appeared to move toward the skin after leaving the abdominal cavity. This revealed that the spread of tumor cells is not random.

The investigators also showed that stem cell transplants could be studied in the fish. It is unknown why transplants of blood-forming stem cells help some cancer patients rebuild healthy blood and yet do not work in other patients. The process was observable in the fish, even down to the single-cell level. This could help reveal how transplanted stem cells embed and build blood.

The researchers say that the fish are optically clear enough to provide single-cell resolution with a confocal microscope. To study various processes, the fish could be crossed with transgenic lines expressing various GFP labels, or transgenic constructs could be directly injected. The scientists believe that the transparent adult zebra fish will be useful for genetic and small-molecule-based screens, thus allowing detailed in vivo study of stem cell and cancer biology in a vertebrate that has relevance to human biology.


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