PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin | Zendy

Khalid Bajou | Zendy; Stéphanie Herkenne | Zendy; Victor L. Thijssen | Zendy; Salvino D’Amico | Zendy; Ngoc-Quynh-Nhu Nguyen | Zendy; Ann Bouché | Zendy; Sébastien P. Tabruyn | Zendy; Mohammed Srahna | Zendy; Jean-Yves Carabin | Zendy; Olivier Nivelles | Zendy; Cécile Paques | Zendy; Ivo Cornelissen | Zendy; Michelle Lion | Zendy; Agnès Noël | Zendy; Ann Gils | Zendy; Stefan Vinckier | Zendy; Paul Declerck | Zendy; Arjan W. Griffioen | Zendy; Mieke Dewerchin | Zendy; Joseph Martial | Zendy; Peter Carmeliet | Zendy; Ingrid Struman | Zendy

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PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin

Author(s) -

Khalid Bajou,

Stéphanie Herkenne,

Victor L. Thijssen,

Salvino D’Amico,

Ngoc-Quynh-Nhu Nguyen,

Ann Bouché,

Sébastien P. Tabruyn,

Mohammed Srahna,

Jean-Yves Carabin,

Olivier Nivelles,

Cécile Paques,

Ivo Cornelissen,

Michelle Lion,

Agnès Noël,

Ann Gils,

Stefan Vinckier,

Paul Declerck,

Arjan W. Griffioen,

Mieke Dewerchin,

Joseph Martial,

Peter Carmeliet,

Ingrid Struman

Publication year - 2014

Publication title -

nature medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.536

H-Index - 547

eISSN - 1546-170X

pISSN - 1078-8956

DOI - 10.1038/nm.3552

Subject(s) - urokinase receptor , angiogenesis , plasminogen activator , endocrinology , medicine , prolactin , chemistry , cancer research , receptor , antifibrinolytic , urokinase , hormone , blood loss , surgery , tranexamic acid

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.

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