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

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...

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Autores principales: Kwaan, H C, Wang, J, Svoboda, K, Declerck, P J
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374508/
https://www.ncbi.nlm.nih.gov/pubmed/10817507
http://dx.doi.org/10.1054/bjoc.2000.1207
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author Kwaan, H C
Wang, J
Svoboda, K
Declerck, P J
author_facet Kwaan, H C
Wang, J
Svoboda, K
Declerck, P J
author_sort Kwaan, H C
collection PubMed
description 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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spelling pubmed-23745082009-09-10 Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis Kwaan, H C Wang, J Svoboda, K Declerck, P J Br J Cancer Regular Article 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 Nature Publishing Group 2000-05 2000-04-27 /pmc/articles/PMC2374508/ /pubmed/10817507 http://dx.doi.org/10.1054/bjoc.2000.1207 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Kwaan, H C
Wang, J
Svoboda, K
Declerck, P J
Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title_full Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title_fullStr Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title_full_unstemmed Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title_short Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
title_sort plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374508/
https://www.ncbi.nlm.nih.gov/pubmed/10817507
http://dx.doi.org/10.1054/bjoc.2000.1207
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