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A UMU study sees in real time the evolution of the metastasis in the zebrafish (24/11/2017)

The research group Immunity, Inflammation and Cancer (IIC), led by Victoriano Mulero, has managed to follow in real time the evolution of a metastasis, that is, the invasion of the tumor to other tissues, in order to find possible therapeutic targets.

The article, published in the International Journal of Cancer, has studied in vivo the aggressiveness of melanoma, that is, of the most aggressive tumor of the skin, using as a model the zebrafish, which by its transparency allows to see at all times how it develops. tumor.

To carry out the research, the group transplanted human melanoma cells into zebrafish larvae.

By means of said xenotransplantation (transplantation between two different species) we see how they perform metastasis, that is, simulating the evolution that occurs within the patient.

Melanoma originates in melanocytes, the cells that pigment the skin.

These are responsible for producing melanin, a pigment that increases to protect us from solar radiation, and is responsible for us tanning.

The problem is that a prolonged exposure to the sun can produce mutations in these melanocytes, transforming into a tumor called melanoma.

This type of cancer in a late diagnosis can spread to other parts of the body, that is, metastasize.

Víctoriano Mulero, leader of the UMU group, points out that "at this point the therapies are not usually well responded to".

Therefore, prevention is fundamental.

But just as important is knowing the mechanisms involved in this invasion of other tissues.

The researcher is committed to finding therapeutic targets, proteins on which a drug acts so that metastasis can be prevented.

The study starts with a xenotransplant: they transplant human melanoma cells to zebrafish larvae.

"The transparency of the larvae is used, and human cells are stained with a dye, which can be used to observe the metastasis and interaction of blood vessels and the immune system, which regulates their development. of the tumor in vivo, the zebrafish is an ideal model because it has a very similar response, "says the researcher.

The analysis reveals that it is a protein that increases the resistance of melanoma cells: bcl-xL.

Also, it induces the production of interleukin 8 (CXCL8) that promotes the aggressiveness of the tumor, favors the formation of blood vessels and metastasis.

The biologist explains that these results have therapeutic interest.

"In the case of tumors that have high levels of these proteins bcl-xL and interleukin 8 the patient's prognosis is bad," he says.

On the other hand, although each type of tumor is different, the transfer of this model to other types of cancer in the future could be studied.

Not only have they researched larvae, but they have also developed models with adult zebrafish.

Using the latter, the next step is to delve into the mechanisms involved in metastasis, specifically how the molecules that regulate inflammation can promote or prevent it.

The scientist positions the main controversy on this point: "There is a lot of debate here about whether immunity and inflammation favor the tumor or, on the contrary, it damages it, everything depends on the type of response that occurs."

The financing of the project has been made through U-Impact, a UMU program with European funding that seeks to increase the number of doctors within the research teams.

Among the beneficiaries of this help is Dr. Chiara Gabellini, first author of this article.

In order to carry out this research, we have had the collaboration of the Italian group led by Donatella del Bufalo, director of the doctorate of this researcher.

From this cooperation, it has been possible to combine the melanoma models of the Italian team with the in vivo model of the zebrafish studied, in the words of Victoriano Mulero: "Where there are interactions, wealth comes"

Source: Universidad de Murcia

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