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

doi:10.1160/TH03-12-0784

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(03): 438-449
DOI: 10.1160/TH03-12-0784

Theme Issue Review Article

Schattauer GmbH

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

Michelle K.V. Durand

¹Department of Molecular Biology, Aarhus University, Denmark

,

Julie S. Bødker

¹Department of Molecular Biology, Aarhus University, Denmark

,

Anni Christensen

¹Department of Molecular Biology, Aarhus University, Denmark

,

Daniel M. Dupont

¹Department of Molecular Biology, Aarhus University, Denmark

,

Martin Hansen

¹Department of Molecular Biology, Aarhus University, Denmark

,

Jan K. Jensen

¹Department of Molecular Biology, Aarhus University, Denmark

,

Signe Kjelgaard

¹Department of Molecular Biology, Aarhus University, Denmark

,

Lisa Mathiasen

¹Department of Molecular Biology, Aarhus University, Denmark

,

Katrine E. Pedersen

¹Department of Molecular Biology, Aarhus University, Denmark

,

Sune Skeldal

¹Department of Molecular Biology, Aarhus University, Denmark

,

Troels Wind

¹Department of Molecular Biology, Aarhus University, Denmark

,

Peter A. Andreasen

¹Department of Molecular Biology, Aarhus University, Denmark

› Author Affiliations

Abstract

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.

Keywords

Proteases - serpins - desmoplasia - angiogenesis

Full Text

References

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