Journal article

The fibrinolysis inhibitor alpha(2)-antiplasmin restricts lymphatic remodelling and metastasis in a mouse model of cancer

Sophie Paquet-Fifield, Sally Roufail, You-Fang Zhang, Trifina Sofian, David J Byrne, Paul B Coughlin, Stephen B Fox, Steven A Stacker, Marc G Achen

GROWTH FACTORS | TAYLOR & FRANCIS LTD | Published : 2017

Abstract

Remodelling of lymphatic vessels in tumours facilitates metastasis to lymph nodes. The growth factors VEGF-C and VEGF-D are well known inducers of lymphatic remodelling and metastasis in cancer. They are initially produced as full-length proteins requiring proteolytic processing in order to bind VEGF receptors with high affinity and thereby promote lymphatic remodelling. The fibrinolytic protease plasmin promotes processing of VEGF-C and VEGF-D in vitro, but its role in processing them in cancer was unknown. Here we explore plasmin's role in proteolytically activating VEGF-D in vivo, and promoting lymphatic remodelling and metastasis in cancer, by co-expressing the plasmin inhibitor α2-antip..

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