| Literature DB >> 24929950 |
Khalid Bajou1, Stephanie Herkenne1, Victor L Thijssen2, Salvino D'Amico3, Ngoc-Quynh-Nhu Nguyen3, Ann Bouché4, Sébastien Tabruyn3, Mohammed Srahna3, Jean-Yves Carabin3, Olivier Nivelles3, Cécile Paques3, Ivo Cornelissen4, Michelle Lion3, Agnès Noel5, Ann Gils6, Stefan Vinckier4, Paul J Declerck6, Arjan W Griffioen7, Mieke Dewerchin4, Joseph A Martial1, Peter Carmeliet8, Ingrid Struman3.
Abstract
The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss of PAI-1 abrogated the antitumoral and antiangiogenic effects of 16K PRL. PAI-1 bound the ternary complex PAI-1-urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR), thereby exerting antiangiogenic effects. By inhibiting the antifibrinolytic activity of PAI-1, 16K PRL also protected mice against thromboembolism and promoted arterial clot lysis. Thus, by signaling through the PAI-1-uPA-uPAR complex, 16K PRL impairs tumor vascularization and growth and, by inhibiting the antifibrinolytic activity of PAI-1, promotes thrombolysis.Entities:
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Year: 2014 PMID： 24929950 DOI： 10.1038/nm.3552
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440