Thromb Haemost 2008; 100(06): 1041-1046
DOI: 10.1160/TH08-04-0266
Theme Issue Article
Schattauer GmbH

Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)

Ulrik A. Lademann
1   Department of Disease Biology, Section for Biomedicine, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C., Denmark
,
Maria Unni Rømer
1   Department of Disease Biology, Section for Biomedicine, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C., Denmark
› Institutsangaben
Financial support: This work was supported by grants from The IMK Foundation, Købmand I Odense Johann og Hanne Weimann, f. Seedorff Legat, the Danish Cancer Society, The A.P. Møller Foundation for the Advancement of Medical Science, The Danish Foundation for Cancer Research and The Danish Medical Research Council.
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Publikationsverlauf

Received: 29. April 2008

Accepted after major revision: 09. November 2008

Publikationsdatum:
23. November 2017 (online)

Summary

Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase-type plasminogen activator (uPA) observed in tumours; however, several lines of evidence suggest that PAI-1 may contribute directly to the pathology of the disease. PAI-1 has been reported to have an effect on most of the basic cellular processes including cell adhesion, cell migration, cell invasion, and cell proliferation and increasing numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells.A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.

 
  • References

  • 1 Beyer BCM, Heiss MM, Simon EH. et al. Urokinase system expression in gastric carcinoma – Prognostic impact in an independent patient series and first evidence of predictive value in preoperative biopsy and intestinal metaplasia specimens. Cancer 2006; 106: 1026-1035.
  • 2 Grondahl H, Christensen IJ, Rosenquist C. et al. High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res 1993; 53: 2513-2521.
  • 3 Hofmann R, Lehmer A, Buresch M. et al. Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer 1996; 78: 487-492.
  • 4 Pedersen H, Brunner N, Francis D. et al. Prognostic impact of urokinase, urokinase receptor, and type-1 plasminogen-activator inhibitor in squamous and large-cell lung-cancer tissue. Cancer Res 1994; 54: 4671-4675.
  • 5 Stahl A, Mueller BM. Melanoma cell migration on vitronectin: Regulation by components of the plasminogen activation system. Int J Cancer 1997; 71: 116-122.
  • 6 Bajou K, Noel A, Gerard RD. et al. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nature Med 1998; 04: 923-928.
  • 7 Gutierrez LS, Schulman A, Brito-Robinson T. et al. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res 2000; 60: 5839-5847.
  • 8 Maillard C, Jost M, Romer MU. et al. Host plasmi-nogen activator inhibitor-1 promotes human skin carcinoma progression in a stage-dependent manner. Neoplasia 2005; 07: 57-66.
  • 9 Palmieri D, Lee JW, Juliano RL, Church FC. Plas-minogenActivator Inhibitor-1 and -3 Increase Cell Adhesion and Motility of MDA-MB-435 Breast Cancer Cells. J Biol Chem 2002; 277: 40950-40957.
  • 10 Andreasen PA. PAI-1 - a potential therapeutic target in cancer. Curr Drug Targets 2007; 08: 1030-1041.
  • 11 Cao C, Lawrence DA, Li Y. et al. Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration. EMBO J 2006; 25: 1860-1870.
  • 12 Huntington JA, Read RJ, Carrell RW. Structure of a serpin-protease complex shows inhibition by deformation. Nature 2000; 407: 923-926.
  • 13 Cubellis MV, Wun TC, Blasi F. Receptor-mediated internalization and degradation of urokinase is caused by its specific inhibitor PAI-1. EMBO J 1990; 09: 1079-1085.
  • 14 Nykjaer A, Conese M, Christensen EI. et al. Recycling of the urokinase receptor upon internalization of the uPA:serpin complexes. EMBO J 1997; 16: 2610-2620.
  • 15 Heegaard CW, Simonsen AC, Oka K. et al. Very low density lipoprotein receptor binds and mediates endocytosis of urokinase-type plasminogen activatortype-1 plasminogen activator inhibitor complex. J Biol Chem 1995; 270: 20855-20861.
  • 16 Stefansson S, Muhammad S, Cheng XF. et al. Plasminogen activator inhibitor-1 contains a cryptic high affinity binding site for the low density lipoprotein receptor-related protein. J Biol Chem 1998; 273: 6358-6366.
  • 17 Skeldal S, Larsen JV, Pedersen KE. et al. Binding areas of urokinase-type plasminogen activator-plasmi-nogen activator inhibitor-1 complex for endocytosis receptors of the low-density lipoprotein receptor family, determined by site-directed mutagenesis. FEBS J 2006; 273: 5143-5159.
  • 18 Webb DJ, Thomas KS, Gonias SL. Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growth. J Cell Biol 2001; 152: 741-752.
  • 19 Campana WM, Li X, Dragojlovic N. et al. The low-density lipoprotein receptor-related protein is a pro-survival receptor in Schwann cells: possible implications in peripheral nerve injury. J Neurosci 2006; 26: 11197-1207.
  • 20 Montel V, Gaultier A, Lester RD. et al. The low-density lipoprotein receptor-related protein regulates cancer cell survival and metastasis development. Cancer Res 2007; 67: 9817-9824.
  • 21 Germer M, Kanse SM, Kirkegaard T. et al. Kinetic analysis of integrin-dependent cell adhesion on vitronectin--the inhibitory potential of plasminogen activator inhibitor-1 and RGD peptides. Eur J Biochem 1998; 253: 669-674.
  • 22 Seiffert D, Smith JW. The cell adhesion domain in plasma vitronectin is cryptic. J Biol Chem 1997; 272: 13705-13710.
  • 23 Stefansson S, Lawrence DA. The serpin PAI-1 inhibits cell migration by blocking integrin alpha V beta 3 binding to vitronectin. Nature 1996; 383: 441-443.
  • 24 Lazar MH, Christensen PJ, Du M. et al. Plasminogen Activator Inhibitor-1 Impairs Alveolar Epithelial Repair by Binding to Vitronectin. Am J Respir Cell Mol Biol 2004; 31: 672-678.
  • 25 Deng G, Curriden SA, Hu G. et al. Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the somatomedin B domain of vitronectin. J Cell Physiol 2001; 189: 23-33.
  • 26 Schar CR, Blouse GE, Minor KH. et al. A deletion mutant of vitronectin lacking the somatomedin B domain exhibits residual plasminogen activator inhibitor-1-binding activity. J Biol Chem 2008; 283: 10297-10309.
  • 27 Schar CR, Jensen JK, Christensen A. et al. Characterization of a site on PAI-1 that binds to vitronectin outside of the somatomedin B domain. J Biol Chem 2008; 283: 28487-28496.
  • 28 Chen SC, Henry DO, Reczek PR. et al. Plasminogen activator inhibitor-1 inhibits prostate tumor growth through endothelial apoptosis. Mol Cancer Ther 2008; 07: 1227-1236.
  • 29 Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell 1997; 88: 347-354.
  • 30 Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456-1462.
  • 31 Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407: 770-776.
  • 32 Krammer PH. CD95’s deadly mission in the immune system. Nature 2000; 407: 789-795.
  • 33 Nicholson DW. From bench to clinic with apoptosis-based therapeutic agents. Nature 2000; 407: 810-816.
  • 34 Jaattela M. Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene 2004; 23: 2746-2756.
  • 35 Jaattela M. Escaping cell death: survival proteins in cancer. Exp Cell Res 1999; 248: 30-43.
  • 36 Boudreau N, Sympson CJ, Werb Z. et al. Suppression of ICE and apoptosis in mammary epithelial cells by extra-cellular matrix. Science 1995; 267: 891-893.
  • 37 Raff MC, Barres BA, Burne JF. et al. Programmed Cell-Death and the Control of Cell-Survival - Lessons from the Nervous-System. Science 1993; 262: 695-700.
  • 38 Cheng GZ, Park S, Shu SK. et al. Advances of AKT pathway in human oncogenesis and as a target for anticancer drug discovery. Current Cancer Drug Ta rgets 2008; 08: 2-6.
  • 39 Henson ES, Gibson SB. Surviving cell death through epidermal growth factor (EGF) signal trans-duction pathways: Implications for cancer therapy. Cell Signalling 2006; 18: 2089-2097.
  • 40 Li HC, Fan XL, Houghton J. Tumor microenvironment: The role of the tumor stroma in cancer. J Cell Biochem 2007; 101: 805-815.
  • 41 Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature 2001; 411: 375-379.
  • 42 Usher PA, Thomsen OF, Iversen P. et al. Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue. Int J Cancer 2005; 113: 870-880.
  • 43 Offersen BV, Nielsen BS, Hoyer-Hansen G. et al. The myofibroblast is the predominant plasminogen activator inhibitor-1-expressing cell type in human breast carcinomas. Am J Pathol 2003; 163: 1887-1899.
  • 44 Illemann M, Hansen U, Nielsen HJ. et al. Leadingedge myofibroblasts in human colon cancer express plasminogen activator inhibitor-1. Am J Clin Pathol 2004; 122: 256-265.
  • 45 Lindberg P, Larsson A, Nielsen BS. Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma. Int J Cancer 2006; 118: 2948-2956.
  • 46 Hundsdorfer B, Zeilhofer HF, Bock KP. et al. Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity - clinical relevance and prognostic value. J Cranio-Maxillofacial Surg 2005; 33: 191-196.
  • 47 Providence K, Higgins S, Mullen A. et al. SER-PINE1 (PAI-1) is deposited into keratinocyte migration “trails” and required for optimal monolayer wound repair. Arch Dermatol Res 2008; 300: 303-310.
  • 48 Kwaan HC, Wang J, Svoboda K. et al. Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis. Br J Cancer 2000; 82: 1702-1708.
  • 49 Kimura M, Soeda S, Oda M. et al. Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide. J Neurosci Res 2000; 62: 781-788.
  • 50 Soeda S, Shinomiya K, Ochiai T. et al. Plasminogen activator inhibitor-1 aids nerve growth factor-induced differentiation and survival of pheochromocytoma cells by activating both the extra-cellular signal-regulated kinase and c-Jun pathways. Neuroscience 2006; 141: 101-108.
  • 51 Soeda S, Oda M, Ochiai T. et al. Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells. Mol Brain Res 2001; 91: 96-103.
  • 52 Gill JS, Schenone AE, Podratz JL. et al. Autocrine regulation of neurite outgrowth from PC12 cells by nerve growth factor. Mol Brain Res 1998; 57: 123-131.
  • 53 Greene LA, Tischler AS. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth-factor. Proceedings of the National Academy of Sciences of the United States of America 1976; 73: 2424-2428.
  • 54 Zielke A, Bresalier RS, Siperstein AE. et al. A unique allogenic model of metastatic pheochromocytoma: PC12 rat pheochromocytoma xenografts to nude mice and establishment of metastases-derived PC12 variants. Clin Exp Metastasis 1998; 16: 341-352.
  • 55 Lademann U, Romer MU, Jensen PB. et al. Malignant transformation of wild-type but not plasminogen activator inhibitor-1 gene-deficient fibroblasts decreases cellular sensitivity to chemotherapy-mediated apoptosis. Eur J Cancer 2005; 417: 1095-100.
  • 56 Romer MU, Kirkebjerg DA, Knud LJ. et al. Indication of a role of plasminogen activator inhibitor type I in protecting murine fibrosarcoma cells against apoptosis. Thromb Haemost 2005; 94: 859-866.
  • 57 Romer MU, Larsen L, Offenberg H. et al. Plasminogen activator inhibitor 1 protects fibrosarcoma cells from etoposide-induced apoptosis through activation of the PI3K/Akt cell survival pathway. Neoplasia 2008; 10: 1083-1091.
  • 58 Han BH, Holtzman DM. BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J Neurosci 2000; 20: 5775-5781.
  • 59 Buisson A, Nicole O, Docagne F. et al. Up-regulation of a serine protease inhibitor in astrocytes mediates the neuroprotective activity of transforming growth factor beta 1. Faseb J 1998; 12: 1683-1691.
  • 60 Gabriel C, Ali C, Lesne S. et al. Transforming growth factor alpha-induced expression of type-1 plas-minogen activator inhibitor in astrocytes rescues neurons from excitotoxicity. Faseb J 2003; 16: 277-279.
  • 61 Thornton P, Pinteaux E, Allan SM. et al. Matrix metalloproteinase-9 and urokinase plasminogen activator mediate interleukin-1-induced neurotoxicity. Mol Cell Neurosci 2008; 37: 135-142.
  • 62 Rossignol P, Luttun A, Martin-Ventura JL. et al. Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques. J Thromb Haemost 2006; 04: 664-670.
  • 63 Rossignol P, Angles-Canos E, Lijnen HR. Plasminogen activator inhibitor-I impairs plasminogen activation-mediated vascular smooth muscle cell apoptosis. Thromb Haemost 2006; 96: 665-670.
  • 64 Horowitz JC, Rogers DS, Simon RH. et al. Plasmi-nogen activation-induced pericellular fibronectin proteolysis promotes fibroblast apoptosis. Am J Respir Cell Mol Biol 2008; 38: 78-87.
  • 65 Al-Fakhri N, Chavakis T, Schmidt-Woll T. et al. Induction of apoptosis in vascular cells by plasminogen activator inhibitor-1 and high molecular weight kininogen correlates with their anti-adhesive properties. Biol Chem 2003; 384: 423-435.
  • 66 Chen YB, Kelm RJ, Budd RC. et al. Inhibition of apoptosis and caspase-3 in vascular smooth muscle cells by plasminogen activator inhibitor type-1. J Cell Biochem 2004; 92: 178-188.
  • 67 Das F, Ghosh-Choudhury N, Venkatesan B. et al. Akt kinase targets association of CBP with SMAD 3 to regulate TGF betainduced expression of plasminogen activator inhibitor-1. J Cell Physiol 2008; 214: 513-527.
  • 68 Kietzmann T, Jungermann K, Gorlach A. Regulation of the hypoxia-dependent plasminogen activator inhibitor I expression by MAP kinases. Thromb Haemost 2003; 89: 666-673.
  • 69 Mukai Y, Wang CY, Rikitake Y, Liao JK. Phosphati-dylinositol 3-kinase/protein kinase Akt negatively regulates plasminogen activator inhibitor type 1 expression in vascular endothelial cells. Am J Physiol-Heart Circul Physiol 2007; 292: H1937-H1942.
  • 70 Whitley BR, Beaulieu LM, Carter JC. et al. Phosphatidylinositol 3-kinase/Akt regulates the balance between plasminogen activator inhibitor-1 and urokinase to promote migration of SKOV - 3 ovarian cancer cells. Gynecol Oncol 2007; 104: 470-479.
  • 71 Balsara RD, Castellino FJ, Ploplis VA. A novel function of plasminogen activator inhibitor-1 in modulation of the AKT pathway in wild-type and plasminogen activator inhibitor-1-deficient endothelial cells. J Biol Chem 2006; 281: 22527-22536.
  • 72 Kortlever RM, Higgins PJ, Bernards R. Plas-minogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nature Cell Biol 2006; 08: 877-U155.
  • 73 Alfano D, Iaccarino I, Stoppelli MP. Urokinase signaling through its receptor protects against anoikis by increasing BCL-xL expression levels. J Biol Chem 2006; 281: 17758-17767.
  • 74 Jensen JK, Durand MK, Skeldal S. et al. Construction of a plasminogen activator inhibitor-1 variant without measurable affinity to vitronectin but otherwise normal. FEBS Lett 2004; 556: 175-179.
  • 75 Xu Z, Balsara RD, Gorlatova NV. et al. Conservation of critical functional domains in murine plasminogen activator inhibitor-1. J Biol Chem 2004; 279: 17914-17920.