Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, P.O.Box: 27272, UAE
Angiogenesis, the formation of new blood vessels, is a key event in tumor growth. Targeting angiogenesis remain an attractive therapy to cure cancer. The N terminal fragments of prolactin (16K PRL) is potent angiogenesis inhibitor with demonstrated antitumor effects. The membrane receptor involved in these effects has remained unknown. We identified the Plasminogen Activator Inhibitor type 1 (PAI-1) as a binding partner for 16K PRL. In PAI-1-deficient mice, the antitumor activity of 16K PRL is suppressed unless PAI-1 is restored. At the cell surface, 16K PRL interact with the ternary complex PAI-1/urokinase-type plasminogen activator (uPA)/uPA receptor. PAI-1/16K PRL interaction is mandatory for the antiangiogenic actions of 16K PRL but is detrimental to the antiproteolytic, clot-maintaining function of PAI-1, highlighting an unsuspected role for 16K PRL in fibrinolysis regulat ion.