Let’s Get Together: Fish Hybrids and Melanoma

Bob Marley

While playing soccer in Paris in 1977, legendary reggae composer Bob Marley injured his big toenail, opening up an old wound. Despite removing the nail, his toe got worse. The doctors diagnosed the irregularly shaped, non-healing bruise as melanoma, a type of skin cancer.

The diagnosis of skin cancer is not uncommon; one in every five people will develop skin cancer in the course of their lifetime (“Melanoma,” 2013).

For the vast majority, the diagnosis is treatable and highly survivable. But in Marley’s case, the news was devastating; melanoma is the aggressive cancer responsible for the vast majority of skin cancer deaths, killing one person every hour (“Melanoma,” 2013).

In early stages, like Bob Marley’s case, melanoma is treatable. Amputation is just one of many treatment options, depending on size, location, and severity of the cancer. However, because of his religious beliefs, Bob Marley refused to amputate his toe, leading to his premature death at just 36, after the melanoma spread to his vital organs.

Value of Models

Animal models such as the swordtail-platyfish hybrid are used to better understand how melanoma appears and spreads.

Although there are other fish models used in melanoma research, swordtail-platyfish hybrid models are unique due to their ability to spontaneously develop melanoma.

These hybrids are a second generation cross. First, a pigmented platyfish, Xiphophorus maculates, and a nonpigmented swordtail, Xiphophorus hellerii, are crossed; then, the resulting hybrid is crossed with another swordtail to form a Xiphophorus hybrid that is ¾ swordtail and ¼ platyfish.

These crosses are necessary to combine growth modifying factors from the swordtail with a dominant allele controlling the distribution of melanocytes from the platyfish. In wild platyfish, these melanocytes do not produce pigmentation, meaning these fish cannot get melanoma. However, in the presence of the swordtail’s growth factors, these melanocytes will produce melanin, which leads to melanoma. In essence, the best genes (or worst, depending on how you think about it) are taken from each species and combined in these hybrids, making them extremely prone to melanoma. Additionally, the type, progression, and metastasis patterns of the melanoma in fish are often similar to humans (Meenhard, 2013).

[Photo: Xiphophorus maculatus offspring by Ude, License: GNU Free Documentation License; Photo: Type of fish that was flown on STS-90 by NASA, License: Public Domain]
[Photo: Xiphophorus maculatus offspring by Ude, License: GNU Free Documentation License; Photo: Type of fish that was flown on STS-90 by NASA, License: Public Domain]
Using swordtail-platyfish hybrids, scientists found a proto-oncogene – a normal gene that causes cancer when turned on – that causes spontaneous melanoma formation in these fish. This gene, XMRK, or Xiphophorus Melanoma Receptor Kinase, resides on the sex chromosome and allows melanoma to be inherited.

The importance of studying XMRK in swordtail-platyfish models is the universal commonalities among proto-oncogenes in different organisms, meaning a similar gene with similar inheritance patterns could very well be what causes melanoma in humans.

The End of an Era?

Even with all the advances made using swordtail-platyfish models, these animals are already being phased out for Zebrafish models, which have many practical advantages such as external fertilization, which allows for analysis of embryo development. In addition, medakas, or Japanese rice fish, are starting to gain prominence as an alternative melanoma model because they can also express the XMRK gene.

In the future, a multi-pronged approach using a combination of new drugs to target each specific melanoma-inducing protein would be productive in halting the disease. Dr. Keith Flaherty of the Dana-Farber/Harvard Cancer Center is just one of many optimistic oncologists who believe this new method, which has worked against H.I.V., would be just as effective against melanoma. “‘We just need,’ Dr. Flaherty said, ‘to find the right combination’” (Harmon, 2010).

This method of treatment could call for multiple models, some that have not even been identified yet. This impetus will invariably lead to the discovery of more complete and diverse animal models. For now, the swordtail-platyfish hybrids are a great step beyond conventional models and are music to the ears of melanoma patients, much like Bob Marley’s music which transcended race and time to serve as inspiration to millions.

In Brief:

Works Cited

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