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
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..View full abstract
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This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (to MGA and SAS) and the Operational Infrastructure Support Program of the Victorian Government.