Transparent Fish Reveal Secrets of Tumor Spread

By Jennifer Bell

on Tuesday, December 3, 2013

Pictured: Casper zebrafish

Physician and cell biologist Richard White has generated a transparent and stripeless strain of zebrafish to study how tumors develop the capacity to metastasize to new organs.

This image shows a zebrafish with a melanoma that has spread, or metastasized, throughout the body. The tumors are clearly visible because they produce a marker protein that gives off a green glow, and the fish, unlike ordinary zebrafish, is see-through.

Memorial Sloan Kettering physician and researcher Richard M. White generated this transparent and stripeless strain of zebrafish to allow researchers to visualize the growth and spread of tumors in a whole animal. He is using the fish, which he named Casper after the cartoon ghost, to study metastasis – the process whereby cancer cells escape from a primary tumor, enter the bloodstream, and take root in a new location to propagate additional tumor growth.

Although metastasis is responsible for the majority of cancer deaths, we know very little about how it happens or how to prevent it. “As an oncologist I found it incredible that survival rates from metastatic cancer are essentially unchanged since the 1960s,” says Dr. White. Frustrated by the slow rate of progress, he adopted an innovative approach to the problem of metastasis using zebrafish and evolutionary biology methods.

Model Subject

Zebrafish are emerging as a powerful tool in cancer research. The fish succumb to many of the same cancers as humans, including melanoma and blood cancers. They are also small, cheap, and highly amenable to genetic manipulation, making them an ideal model to systematically screen thousands of genes.

Casper provides the Memorial Sloan Kettering team with a rapid visual readout of metastasis and allows them to probe the complex interplay of genes at work in the tumor cells and in the noncancerous tissues they invade.

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An Evolutionary Idea

Metastasis is a highly unpredictable process, and the genes involved are likely to differ from patient to patient. Dr. White’s ultimate goal is to identify the root causes of metastasis common to all patients.

“There may be a hundred different ways for a tumor to metastasize,” he explains. “Rather than looking at the multitude of individual genes responsible, we are asking, What are the underlying processes that drive the tumor cells to do this?”

Using Casper and other zebrafish models, his team is investigating how tumors evolve the capacity to metastasize. One theory is that stressful conditions within the tumor, such as low oxygen, trigger tumor cells to diversify their genes, allowing them to evolve new traits and exit the tumor.

Dr. White predicts that interfering with tumor evolution, for example by alleviating tumor cell stress, could provide radical new approaches to treat cancer that would not eliminate the tumor but would prevent metastasis.

In September 2013, he was awarded a $1.5 million National Institutes of Health Director’s New Innovator Award to pursue his evolutionary approach to metastasis. These prestigious awards are specifically designed to support innovative and high-risk research.

Read a story in The Scientist co-authored by Dr. White to learn more about how zebrafish are advancing our understanding of cancer development.

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I find this study very interesting. I am a cancer patient at mskcc since 2004 and have had malignant cancer called MFH which keeps on coming back and hope to find a cure this seems hopeful to me please keep up the research

This is a fantastic article. My daughter is in remission from Neuroblastoma. Solid tumors which metastasized to her bone as well as becoming present in liquid marrow and then spreading throughout her body. Very little research has e
Been done on this particular type of pediatric cancer so I am very hopeful that this study will answer some questions that may help this this disease. Most children are diagnosed at Stage 4 and most will have an incident of relapse. This is exciting research!

Applauding the research and passion of dr white and all the research lab pros at mskcc. Read something about zebra fish getting melanoma and other fish last year most probably to global warming. At much higher rates. Amazing ! Thank you mskcc. :).

As always... thoroughly impressed with Dr. White and his team's dedication and great work. Congratulations on this well deserved award that will allow this important research to continue.

The 62 yr cancer study in J Nat med Ass 2001,v93,490-3, seaton K proves that the level >4.7%. of serum albumin controls all cancers via stabilizing the genome, including P53 anti cancer gene network that also controls aging. This finding was published by Dr ken seaton in "Breaking the Devil's Circle" 1986 and at the press conference Sydney Australia 1986 yet not understood or hidden . How many have died and suffered because of this ignorance?

Ken Seaton I tried to find the above Journal article you mentioned above but couldn't. I'm an 18 yr brain tumor survivor. P53 was an interesting genetic component of the pathology. I received excellent radiation and Neurosurgery at MSKCC now followed at MGH. I would like to read the article. If you can post a link to the journal article I would be appreciative thanks keep up getting the word out. I did all of my own research, read studies, articles & I believe that is particularly why I am still alive.

If oxygen deprivation is to be prevented, why not give hydrogen peroxide intravenously. My naturopath alternative medicine Dr. does exactly that.

I applaud you for thinking out of the box. Have you heard of UC Berkley's gamers group using their gaming techniques to solve health issues?

Is this zebrafish a fish that is eaten amongst humans?

Dear B-Queen, some people appear to eat zebrafish, but it is not common. Thanks for your comment!

Dear Dr. White
The research sounds like a great new way to treat cancer patients with cancer that has metastasized. My father is currently a MSKCC patient his and is currently in the last stage of his battle. I lost my mother to Cancer and now my dad is there, I hope this can give more patients another chance to fight for their life.
Thank You.


Melvin Marroquin

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