Known for its antiangiogenic effects, the 16K PRL fragment of prolactin was, until recently, mainly studied to fight against the development of tumours. The team led by Ingrid Struman, a researcher at the University of Liège’s GIGA-Cancer centre, discovered “somewhat by chance” that this fragment also has an effect against thrombosis, i.e. blood clots that can obstruct our vessels. Consequently, this has opened up new opportunities in the study and therapeutic use of this molecule. A path that hadn’t yet been examined up until now.

Who hasn‘t had a cut or a small wound that seemingly wouldn’t stop bleeding? Luckily, nature has thought of everything and provided a mechanism allowing animals and humans not to bleed to death at the slightest injury. Indeed, if we cut ourselves, bleeding stops rapidly in most cases thanks to the aggregation of blood platelets and coagulation, which takes place at the point where the blood vessel is damaged. Among other things, coagulation consists of the formation of blood clots composed of a protein known as fibrin. The mass thus created by the blood platelets and fibrin is then resorbed , after repair of the vessel wall, in order to prevent the formation of thrombi. During this process known as fibrinolysis, the enzyme plasmin dissolves the blood clots. If there is a fault in this process, the blood clots can lead to the obstruction of the blood vessel, i.e. thrombosis. Depending on the location of the blood clot, the consequences can be more or less severe, even fatal, if it prevents the blood from circulating in a vital organ.

Fibrinolysis, a well regulated process!

Besides fibrin, blood clots formed as a result of a wound contain an inactive protein known as plasminogen. It is transformed into plasmin by activators, in particular the tissue plasminogen activator (t-PA), secreted by the vascular endothelium several days after the injury. Once the clot has dissolved, the fibrinolysis process is regulated to stop and the t-PA is inhibited by... the plasminogen activator (PAI-1). “Today, t-PA, or rather a recombinant form of this protein, is the only molecule used in hospitals as a thrombolytic drug when it is necessary to destroy a large clot that is obstructing a vein or an artery”, explains Ingrid Struman, F.R.S.-FNRS research associate and project manager at ULg’s GIGA-Cancer molecular angiogenesis laboratory.

Ingrid Struman has been studying the 16K PRL fragment of prolactin and its role in angiogenesis for the past ten years or so. “We have known for the past 15 years that 16K PRL has antiangiogenic properties and is capable of blocking the growth of blood vessels”, the researcher points out. “Up until now, we have mainly studied it for its antitumoral properties since angiogenesis is essential for tumour growth”, she continues. Indeed, it is thanks to the creation of blood vessels in its close environment that a tumour is ensured of the delivery of resources in oxygen and nutrients required for its development.

From angiogenesis to the dissolving of blood clots...

Within this knowledge on 16K PRL, Ingrid Struman and her team initiated a fundamental research project aimed at finding the mediator molecule for the antiangiogenic and antitumoral effects of this prolactin fragment. “We performed a yeast library screening within the framework of this project. This technique allowed pieces of genes to be expressed by yeasts and to observe which proteins bind to 16K PRL”, Ingrid Struman explains. This is how the researchers identified the protein PAI-1 as the mediator for the effects of 16K PRL. The scientist and her colleagues, in particular doctors Khalid Bajou and Stéphanie Herkenne, undertook a series of experiments with cellular tools and animal models to see whether they could confirm this role of PAI-1.