A study by the UPV/EHU-University of the Basque Country could facilitate the design of more effective tools for detecting tumours. The work has been highlighted as the best of the month by one of the world’s leading chemistry journals: the Journal of the American Chemical Society (Jacs).
Leioa/Spain — The UPV/EHU’s Department of Physical Chemistry and the Biofísika Institute have conducted a multidisciplinary study of the Tn antigen that appears in 90 % of cancers. Two variants that appear to be similar but which have very different shapes in water have been studied.
The Tn antigen appears in 90 % of cancers and is associated with metastasis. That is why they are very promising biomarkers for identifying cancer cells and have become very attractive targets in therapies to fight cancer, explained Emilio José Cocinero, member of the UPV/EHU’s Department of Physical Chemistry and the Biofísika Institute, and one of the lead authors of the work. Antigens are molecules that induce the formation of antibodies because the immune system recognises them as a threat, which means they have the potential to unleash an immune response.
Two apparently similar variants of Tn antigens, which differ only in one serine or threonine amino acid, have been studied in this piece of work. Yet, the scientists have seen that they behave very differently in water. Emilio José Cocinero pointed out that by using an approach that is both experimental and computational, they have shown that the Tn antigen bonded with threonine adopts a rigid shape in solution thanks to a water molecule that helps to stabilise the structure. By contrast, the Tn antigen bonded with serine lacks the structural component and is flexible in solution. These differences were not observed in the gas phase studies and both molecules behaved in exactly the same way, which had made it possible to unequivocally discover, for the first time, the role of water in the three-dimensional structure of these molecules, he added.
The Significance of Water in a Promising Biomarker
To get to know the active role of water more closely, the researchers have been adding water molecules one by one to see how the Tn antigen behaved. They have seen that adding just one water molecule was enough to change the structure of both antigens, and in fact, water became located in various parts of the molecule.
Emilio José Cocinero explained that it was likely that the various shapes of the Tn antigen gave rise to different interactions with cell receptors and antibodies, and the compression of these structures could facilitate the design of more effective detection tools and anticancer drugs. This work is in fact part of a long-term project that aims to try to produce potential vaccines against cancer.
Cocinero added that the major problem with this molecule, the Tn antigen, was that it is naturally present in the body, which meant that the body’s immune response was very low because our body does not perceive it as a foreign body. Yet, what they have seen is that if the concentration of this molecule increases, it means that the cancer has developed. They could now follow the evolution of this molecule to see the degree to which the cancer has developed, he added.
According to Cocinero, the ideal scenario in the future would involve the potential creation of synthetic molecules that are not present in the body and which would have the same structure as the Tn antigen; the body would thus perceive them as foreign bodies, and therefore unleash a greater immune response against cancer cells.