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Plasminogen activator inhibitor-1 and tumour growth, invasion, and metastasis

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Fibrinolysis and Proteolysis

DOI: http://dx.doi.org/10.1160/TH03-12-0784
Issue: 2004: 91/3 (Mar) pp. 416-635
Pages: 438-449

Plasminogen activator inhibitor-1 and tumour growth, invasion, and metastasis

Michelle K.V. Durand, Julie S. Bødker, Anni Christensen, Daniel M. Dupont, Martin Hansen, Jan K. Jensen, Signe Kjelgaard, Lisa Mathiasen, Katrine E. Pedersen, Sune Skeldal, Troels Wind, Peter A. Andreasen

Department of Molecular Biology, Aarhus University, Denmark

Summary

In recent decades, evidence has been accumulating showing the important role of urokinase-type plasminogen activator (uPA) in growth, invasion, and metastasis of malignant tumours. The evidence comes from results with animal tumour models and from the observation that a high level of uPA in human tumours is associated with a poor patient prognosis. It therefore initially came as a surprise that a high tumour level of the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) is also associated with a poor prognosis, the PAI-1 level in fact being one of the most informative biochemical prognostic markers. We review here recent investigations into the possible tumour biological role of PAI-1, performed by animal tumour models, histological examination of human tumours, and new knowledge about the molecular interactions of PAI-1 possibly underlying its tumour biological functions. The exact tumour biological functions of PAI-1 remain uncertain but PAI-1 seems to be multifunctional as PAI-1 is expressed by multiple cell types and has multiple molecular interactions. The potential utilisation of PAI-1 as a target for anti-cancer therapy depends on further mapping of these functions.