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

H. C. Kwaan*, J. Wang, K. Svoboda, P. J. Declerck

*Corresponding author for this work

Research output: Contribution to journalArticle

120 Scopus citations

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. (C) 2000 Cancer Research Campaign.

Original languageEnglish (US)
Pages (from-to)1702-1708
Number of pages7
JournalBritish Journal of Cancer
Volume82
Issue number10
StatePublished - May 10 2000

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Keywords

  • Apoptosis
  • Plasminogen activator inhibitor 1
  • UPA receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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