An effect against thrombosis
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.
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.
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.