Tadpoles and skin cancer

“Tadpoles could hold the key to developing effective skin cancer drugs,” reports BBC online. The website says scientists have identified a chemical that stops the uncontrolled movement of pigment cells in frogs. As the spreading of pigment cells is behind skin cancer in both humans and frogs it is hoped this chemical could be used in the development of new skin cancer treatments.

The report comes from a study that tested 3,000 chemicals on tadpoles, looking at how these chemicals altered the tadpoles’ pigment patterns as they grew. Researchers found 40 chemicals that had an effect and one that proved particularly effective. They also identified the way in which this chemical acted on the frogs’ cells.

This complex research increases scientists’ understanding of cell movement in tadpole development, but further research is needed to investigate similar processes in mammals. In addition, migration of pigment cells during development is different to the spread of cancerous pigment cells in adult mammals, although there may be similarities.

This research is exciting but a lot more investigation is needed before it is clear whether there are any practical implications in human health.

Where did the story come from?

Matthew Tomlinson and colleagues from the University of East Anglia, the John Innes Centre in Norwich, and Pfizer carried out this research.

The researchers reported funding from Pfizer, the Biotechnology and Biological Sciences Research Council, Universidad Autonoma del Estado de Mexico, and the UK Medical Research Council. The study was published in the peer-reviewed scientific journal Cell.

What kind of scientific study was this?

This was an animal study looking for chemicals that could affect the movement of pigment cells in tadpoles of the Xenopus frog. The pigment cells of interest are called melanophores, which are similar to human pigment cells called melanocytes.

The BBC news report suggests studying these frog melanophores in a lab, could offer a better understanding of how human melanocytes work.

Human melanocyte cells are of interest as the melanoma form of skin cancer is caused by uncontrolled division of pigment cells in the skin. These cancerous pigment cells are particularly invasive and spread through the body easily, causing secondary cancers that make the disease hard to treat. Chemicals that stop migration of these pigment cells might potentially be able to stop cancerous melanoma from spreading through the human body.

The researchers specifically used Xenopus tadpoles in this study because during their development their pigment cells move to specific positions on their body. In normal Xenopus frogs, pigment cells will always form two distinctive stripes seen along the tadpoles’ backs. If a chemical disrupts this movement, these stripes are abnormally formed, making any effects of the chemical easily visible.

The researchers used this property of the frogs’ biology as the basis of an easy test that could screen a large number of different chemicals, identifying ones that affected the formation of these stripes.

This approach is described as a “chemical genomics” approach, in which large numbers of chemical compounds are screened to identify those having a desired effect on an organism or cell, then genetic and other techniques are used to identify which proteins the chemical is affecting. They were able to screen 3,000 substances by incubating frog embryos in chemical solutions and looking at how stripes developed on the maturing tadpoles.

Once the researchers identified chemicals that affected tadpole colouration, they investigated their effects further. In this study the researchers focused on one such chemical, known as NSC84093. This chemical was applied to the embryos at different stages in their development, to see at what point it was having an effect.

They also looked at whether the NSC84093 chemical could affect migration of other types of non-pigment cell that develop from the same ‘parent’ cells lines as the pigment cells. This was of importance, as it would identify which chemicals could prevent pigment cell movement without interfering with the functions of these other cells.

The researchers looked at whether chemicals with similar structures to NSC84093 had similar effects, to identify which parts of chemical’s molecular structure were involved with the effect. Finally, they carried out further experiments on the tadpoles and in test tubes to try determine exactly how NSC84093 was having an effect.

What were the results of the study?

The researchers identified 40 chemical compounds that affected colouration in tadpoles. In particular, the NSC84093 chemical had a dramatic effect on the stripe along the tadpoles’ backs. Instead of a solid line of colour forming, pigments were arranged as separate blocks of colour along the back.

This showed that the pigment cells were not moving correctly, spreading only up to a certain stage, after which they could move no further. The researchers found that the chemical was having its effect early in the migration of the pigment cells, but did not seem to affect other types of cells that developed from the same ‘parent’ cells as the pigment cells.

Further experiments suggested that NSC84093 was having an effect by preventing two proteins from a family called the matrix metalloproteinases (MMPs) from working correctly. Chemically blocking these two specific MMP proteins (MMP-2 and MMP-14) from working in the tadpoles caused disruption in the colouration of the tadpoles.

What interpretations did the researchers draw from these results?

The researchers concluded that their results show the advantages of what they called the ‘chemical genomic’ approach to study developmental processes.

The authors of the study say that they have identified a chemical (NSC84093) that affects pigment cell migration, potentially by blocking the action of MMP proteins. They say their results have implications for developmental biology, the understanding of the roles of MMP proteins in cell migration and the understanding of migration of ‘parent’ cell lineage of the pigment cells.

What does the NHS Knowledge Service make of this study?

This complex research furthers scientists’ understanding of the processes involved in cell movement in developing tadpole embryos. . It is likely that the movement of pigment cells during the development of mammals (including human beings) features similar biochemical pathways, although further research will be needed to investigate this.

Pigment cell migration during development is a different process to migration of cancerous pigment cells in adult animals, although there may be some similarities. More research will be needed to determine whether the NSC84093 chemical that the researchers have identified has a similar effect on pigment cells in developing mammals, and on cancerous pigment cells.

This research is interesting and exciting, but a lot more investigation will be needed to see whether it can have practical implications for human health.