Tadpole soon to help in the fight against cancer and lymphedema

Lymph circulates in our bodies through a complex network of lymphatic vessels, of which little is known. This network is, however, of major importance for the support of the immune system and the fluid in our body. Researchers from the Flanders Interuniversity Institute for Biotechnology (VIB) connected with the Catholic University of Leuven, are the first to indicate that this network can be studied with the help of tadpoles. This accelerates research of the lymphatic vessel network. With tadpoles one can now very quickly identify new genes that play a part in the development and functioning of the lymphatic vessel network. This is a first step in the search for solutions for illnesses related to the lymphatic vessel network, such as cancer and lymphedema.

Lymph: a very important colorless fluid

Fluid and proteins leak out of the blood vessels during blood circulation in the body. A network of lymphatic vessels catches this extravasated colorless fluid, lymph, and transports it back to the blood vessel network. The lymphatic vessel network is of major importance. It is essential for regulating fluid in the body and for the support of the immune system that protects us from pathogenic organisms. Faults in the making or functioning of this network cause many disorders, such as inflammatory and infectious diseases and lymphedema (a swelling caused by water retention). On the other hand, a well-functioning lymphatic vessel network can simplify the spread of cancer cells. A thorough understanding of this network is thus essential for seeking a solution for these diseases.

The search for a suitable model system

As far back as in 1627 Gasparo Asellius discovered the lymphatic vessels as ‘milky veins’. Yet the lymphatic network has not been studied much until now and is therefore as good as unknown, quite amazing seeing its importance for our health. One of the reasons for this lack of study is the fact that there was not a good model system until now. Lymphatic vessels can be studied in mice but this takes time and is extremely complex. Moreover, a study of mice only enables the examination of gene per gene, which complicates revealing the combined action between various genetic factors. For efficient research smaller model organisms are used, such as the zebrafish, which is popular in the study of the blood vessel system. But the zebrafish also offers little comfort, as it does not have any lymphatic vessels.

In the early 20th century studies suggested that tadpoles do have lymphatic vessels. This urged Peter Carmeliet and his research group to examine whether tadpoles can form a suitable model system for the study of the lymphatic vessel network. Tadpoles can easily be genetically modified, which is why they are an ideal model system in which it is relatively easy to identify genes that are important in the development of complex biological structures like lymphatic vessels.

Unraveling the lymphatic vessel system through tadpoles

With their research, the research group op Peter Carmeliet indicated that tadpoles are extremely suitable for the study of lymphatic vessels. To do this they used Prox1, a protein that is essential for the formation of lymphatic vessels. With the help of coloration techniques they visualized the areas in tadpoles where Prox1 is made: the lymphatic vessels. With the same coloration techniques the researchers indicated that the development of lymphatic vessels in tadpoles is comparable to mice and humans. A second part of their research was altering tadpoles in such a way that they make much less Prox1 than normal tadpoles. This resulted in a badly developed lymphatic vessel system, because of which the tadpoles showed signs of lymphedema. It did not have any effect on the blood vessel system.

With these results the VIB researchers are the first to prove that tadpoles are perfect model organisms for the study of lymphatic vessels. In the future tadpoles can be used to identify genes that are important for the development of this complex network. This paves the way for the search for solutions for illnesses caused by faults in the lymphatic vessel network.