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Thromb Haemost 2005; 94(04): 859-866
DOI: 10.1160/TH05-01-0011
DOI: 10.1160/TH05-01-0011
Cellular Proteolysis and Oncology
Indication of a role of plasminogen activator inhibitor type 1 in protecting murine fibrosarcoma cells against apoptosis
Grant support:This work was supported by grants from The Danish Medical Research Council, Danish Cancer Society, Danish Cancer Research Foundation, LEO-Pharma Forskningsfond, The Velux Foundation, The Beckett Foundation, The Foundation of Clinical-experimentel Cancer Research, Especially Concerning Breast Cancer, Desiree og Niels Ydes Foundation, Kathrine og Vigo Skovgaard Foundation and Frode V. Nyegaard og Hustrus Legat.
Further Information
Publication History
Received07 January 2005
Accepted after resubmission14 July 2005
Publication Date:
07 December 2017 (online)
Summary
In a number of cancer types high tumor tissue levels of plasminogen activator inhibitor type 1 (PAI-1) protein are strongly associated with shorter cancer patient survival. This association has been intriguing since PAI-1 is known to inhibit urokinase plasminogen activator (uPA) that converts plasminogen to plasmin, which is actively involved in tumor progression and invasion. In order to further explore the biological role of PAI-1 in cancer, we have prepared fibroblasts from PAI-1 gene deficient mice and from their wild type littermates. From these fibroblasts fibrosarcoma cell lines were established and characterized. Both types of fibroblasts underwent spontaneous transformation as indicated by aneuploidy, immortalization, clonogenicity in soft agar and tumor formationin vivo. While both PAI-1 deficient and PAI-1 expressing cell lines showed similar proliferation ratesin vitro, cells devoid of PAI-1 were significantly more sensitive to apoptotic stimuli. When inoculated subcutaneously into nude mice PAI-1 expressing cells rapidly established tumors, while PAI-1 deficient cells had a significantly longer lag-phase before they started to grow (p<0.0001). The present study suggests that PAI-1,besides its uPA inhibiting function, has a role in cancer progression by protecting tumor cells from undergoing apoptosis.
* These authors are not affiliated to a particular institution
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