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ABSTRACT Plasminogen activator inhibitor 1 (PAI-1) has been found to be a bad prognostic factor in a number of tumours but the reason has not been fully explained. The human prostate cancer

cell line PC-3 and the human promyelocytic leukaemia cell line HL-60 were used in this study to determine the effect of PAI-1 on spontaneous and induced apoptosis in culture. Apoptosis was

induced with camptothecin or etoposide. Addition of a stable variant of PAI-1 or wild-type PAI-1 to these cells resulted in a significant inhibition of apoptosis. In contrast, both the

latent form of PAI-1 and the stable variant of PAI-1 inactivated by a specific neutralizing monoclonal antibody, or the stable variant of PAI-1 in a complex with recombinant urokinase did

not inhibit apoptosis. This indicated that the inhibitory activity of PAI-1 was required for its anti-apoptotic effect but the urokinase-type plasminogen activator receptor was not involved.

These findings provide an explanation for the bad prognostic correlation of high PAI-1 levels in tumours. The anti-apoptotic effect was also found in non-tumoural cells including human

umbilical vein endothelial cells and the benign human breast epithelial cell line MCF-10A, suggesting that this is a novel physiologic function of PAI-1. © 2000 Cancer Research Campaign

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32380–32388 CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematology/Oncology, Department of Medicine, Northwestern University

Medical School, Chicago, 60611, IL, USA H C Kwaan, J Wang & K Svoboda * Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke

Universiteit Leuven, E. van Evenstraat 4, Leuven, B-3000, Belgium P J Declerck Authors * H C Kwaan View author publications You can also search for this author inPubMed Google Scholar * J

Wang View author publications You can also search for this author inPubMed Google Scholar * K Svoboda View author publications You can also search for this author inPubMed Google Scholar * P

J Declerck View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS From twelve months after its original publication, this work is

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Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kwaan, H., Wang, J., Svoboda, K. _et al._ Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of

apoptosis. _Br J Cancer_ 82, 1702–1708 (2000). https://doi.org/10.1054/bjoc.2000.1207 Download citation * Received: 09 September 1999 * Revised: 18 January 2000 * Accepted: 26 January 2000 *

Published: 21 April 2000 * Issue Date: 01 May 2000 * DOI: https://doi.org/10.1054/bjoc.2000.1207 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * apoptosis * plasminogen activator inhibitor 1 * uPA receptor