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Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis

British Journal of Cancer volume 82, pages 1702–1708 (2000)Cite this article

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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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Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago, 60611, IL, USA

    H C Kwaan, J Wang & K Svoboda

  2. Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, E. van Evenstraat 4, Leuven, B-3000, Belgium

    P J Declerck

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  1. H C Kwaan
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  2. J Wang
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  3. K Svoboda
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  4. P J Declerck
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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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

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Keywords

  • apoptosis
  • plasminogen activator inhibitor 1
  • uPA receptor

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