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Review

Characteristics of the level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

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Pages 947-962 | Published online: 09 Jan 2014

References

  • Schmitt M, Harbeck N, Thomssen C et al. Clinical impact of the plasminogen activation system in tumour invasion and metastasis: prognostic relevance and target for therapy. Thromb. Haemost.78, 285–296 (1997).
  • Schmitt M, Jänicke F, Graeff H. Tumour-associated proteases. Fibrinolysis6(Suppl. 4), 3–26 (1992).
  • Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv. Cancer Res.44, 139–266 (1985).
  • Rijken DC. Plasminogen activators and plasminogen activator inhibitors: biochemical aspects. Baillieres Clin. Haematol.8, 291–312 (1995).
  • Nijziel MR, van Oerle R, Hillen HF, Hamulyák K. From Trousseau to angiogenesis: the link between the haemostatic system and cancer. Neth. J. Med.64, 403–410 (2006).
  • Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br. J. Haematol.129, 307–321 (2005).
  • Christensen LR, MacLeod CM. A proteolytic enzyme of serum: characterisation, activation, and reaction with inhibitors. J. Gen. Physiol.28, 559–583 (1945).
  • Lewis JH, Ferguson JH. Studies on a proteolytic enzyme system of the blood. Activation of profibrinolysin by serum fibrinolysokinase. Proc. Soc. Exp. Biol. Med.78, 184–188 (1951).
  • Williams JR. The fibrinolytic activity of urine. Br. J. Exp. Pathol.32, 530–537 (1951).
  • Ploug J, Kjeldgaard NO. Isolation of a plasminogen activator (urokinase) from urine. Arch. Biochem. Biophys.62, 500–501 (1956).
  • Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature261, 595–597 (1976).
  • Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase from human plasma. J. Biol. Chem.257, 3276–3283 (1982).
  • Tissot JD, Schneider P, Hauert J, Ruegg M, Kruithof EK, Bachmann F. Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase. J. Clin. Invest.70, 1320–1323 (1982).
  • Wu M, Arimura GK, Yunis AA. Purification and characterization of a plasminogen activator secreted by cultured human pancreatic carcinoma cells. Biochemistry16, 1913–1908 (1977).
  • Svanberg L, Astedt B. Release of plasminogen activator from normal and neoplastic endometrium. Experientia35, 818–819 (1979).
  • Markus G, Takita H, Camiolo SM, Corasanti JG, Evers JL, Hobika GH. Content and characterization of plasminogen activators in human lung tumours and normal lung tissue. Cancer Res.40, 841–848 (1980).
  • Corasanti JG, Celik C, Camiolo SM et al. Plasminogen activator content of human colon tumours and normal mucosae: separation of enzymes and partial purification. J. Natl Cancer Inst.65, 345–351 (1980).
  • Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J. Cell. Biol.100, 86–92 (1985).
  • del Rosso M, Dini G, Fibbi G. Receptors for plasminogen activator, urokinase, in normal and Rous sarcoma virus-transformed mouse fibroblasts. Cancer Res.45, 630–636 (1985).
  • van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. J. Biol. Chem.259, 14914–14921 (1984).
  • Kawano T, Morimoto K, Uemura Y. Urokinase inhibitor in human placenta. Nature217, 253–254 (1968).
  • Kruithof EK, Baker MS, Bunn CL. Biological and clinical aspects of plasminogen activator inhibitor type 2. Blood86, 4007–4024 (1995).
  • Suzuki M, Kobayashi H, Kanayama N et al. Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J. Biol. Chem.279(15), 14899–14908 (2004).
  • Moran P, Li W, Fan B, Vij R, Eigenbrot C, Kirchhofer D. Pro-urokinase-type plasminogen activator is a substrate for hepsin. J. Biol. Chem.281(41), 30439–30446 (2006).
  • Beaufort N, Seweryn P, de Bentzmann S et al. Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.Biochem. J.428(3), 473–482 (2010).
  • Iakhiaev AV, Nalian A, Koenig K, Idell S. Thrombin-thrombomodulin inhibits prourokinase-mediated pleural mesothelial cell-dependent fibrinolysis. Thromb. Res.120(5), 715–725 (2007).
  • Zorio E, Gilabert-Estelles J, Espana F, Ramon LA, Cosin R, Estelles A. Fibrinolysis: the key to new pathogenetic mechanisms. Curr. Med. Chem.15(9), 923–929 (2008).
  • Fevang B, Eugen-Olsen J, Yndestad A et al. Enhanced levels of urokinase plasminogen activator and its soluble receptor in common variable immunodeficiency. Clin. Immunol.131(3), 438–446 (2009).
  • Miralles F, Parra M, Caelles C, Nagamine Y, Felez J, Munoz-Canoves P. UV irradiation induces the murine urokinase-type plasminogen activator gene via the c-jun n-terminal kinase signaling pathway: requirement of an AP1 enhancer element. Mol. Cell. Biol.18(8), 4537–4547 (1998).
  • Angenete E, Langenskiold M, Palmgren I, Falk P, Oresland T, Ivarsson ML. uPA and PAI-1 in rectal cancer – relationship to radiotherapy and clinical outcome. J. Surg. Res.153(1), 46–53 (2009).
  • Das R, Mahabeleshwar GH, Kundu GC. Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J. Biol. Chem.279(12), 11051–11064 (2004).
  • Szabo H, Novak Z, Bauer H et al. Regulation of proteolytic activity induced by inflammatory stimuli in lung epithelial cells. Cell. Mol. Biol.51(Suppl. OL), 729–735 (2005).
  • Ulisse S, Baldini E, Sorrenti S, D’armiento M. The urokinase plasminogen activator system: a target for anti-cancer therapy. Curr. Cancer Drug Targets9(1), 32–71 (2009).
  • Killeen SD, Andrews EJ, Wang JH et al. Inhibition of urokinase plasminogen activator with a novel enzyme inhibitor, WXC-340, ameliorates endotoxin and surgery-accelerated growth of murine metastases. Br. J. Cancer96(2), 262–268 (2007).
  • Zhao Y, Lyons CE Jr, Xiao A et al. Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochem. Biophys. Res. Commun.369(4), 1215–1220 (2008).
  • Matsuoka H, Sisson TH, Nishiuma T, Simon RH. Plasminogen-mediated activation and release of hepatocyte growth factor from extracellular matrix. Am. J. Respir. Cell Mol. Biol.35(6), 705–713 (2006).
  • Binder BR, Mihaly J, Prager GW. uPAR–uPA–PAI-1 interactions and signaling: a vascular biologist’s view. Thromb. Haemost.97(3), 336–342 (2007).
  • Tarui T, Akakura N, Majumdar M et al. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin α v β 3 induces signal transduction and enhances plasminogen activation. Thromb. Haemost.95(3), 524–534 (2006).
  • Franco P, Vocca I, Carriero MV et al. Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and α v β 5 integrin. J. Cell Sci.119(Pt 16), 3424–3434 (2006).
  • Crippa MP. Urokinase-type plasminogen activator. Int. J. Biochem. Cell Biol.39(4), 690–694 (2007).
  • Alfano D, Iaccarino I, Stoppelli MP. Urokinase signaling through its receptor protects against anoikis by increasing bcl-xl expression levels. J. Biol. Chem.281(26), 17758–17767 (2006).
  • Aguirre Ghiso JA. Inhibition of FAK signaling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo.Oncogene21(16), 2513–2524 (2002).
  • Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G. The putative tumor suppressor LRP1b, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J. Biol. Chem.276(31), 28889–28896 (2001).
  • Czekay RP, Aertgeerts K, Curriden SA, Loskutoff DJ. Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J. Cell. Biol.160(5), 781–791 (2003).
  • Turkmen B, Schmitt M, Schmalfeldt B et al. Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer. Electrophoresis18(5), 686–689 (1997).
  • Przybylowska K, Smolarczyk K, Kulig A et al. Antigen levels of the urokinase-type plasminogen activator and its gene polymorphisms in colorectal cancer. Cancer Lett.181(1), 23–30 (2002).
  • Tsai MH, Chen WC, Chen HY, Tsai FJ. Urokinase gene 3´-UTR T/C polymorphism is associated with oral cancer. J. Clin. Lab. Anal.18(5), 276–279 (2004).
  • Mittal RD, Srivastava DS, Mishra DK. Is urokinase gene 3´-UTR polymorphism associated with prostate cancer? Cancer Biomarkers1(6), 287–292 (2005).
  • Manchanda PK, Bid HK, Mittal RD. Association of urokinase gene 3´-UTR T/C polymorphism with bladder cancer. Urol. Int.77(1), 81–84 (2006).
  • Helenius MA, Saramaki OR, Linja MJ, Tammela TL, Visakorpi T. Amplification of urokinase gene in prostate cancer. Cancer Res.61(14), 5340–5344 (2001).
  • Takahashi T, Suzuki K, Ihara H, Mogami H, Kazui T, Urano T. Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via α(v)β(5) integrin. Semin. Thromb. Hemost.31(3), 356–363 (2005).
  • Chazaud B, Ricoux R, Christov C, Plonquet A, Gherardi RK, Barlovatz-Meimon G. Promigratory effect of plasminogen activator inhibitor-1 on invasive breast cancer cell populations. Am. J. Pathol.160(1), 237–246 (2002).
  • Gils A, Pedersen KE, Skottrup P et al. Biochemical importance of glycosylation of plasminogen activator inhibitor-1. Thromb. Haemost.90(2), 206–217 (2003).
  • Vial D, McKeown-Longo PJ. PAI-1 stimulates assembly of the fibronectin matrix in osteosarcoma cells through crosstalk between the αvβ5 and α5β1 integrins. J. Cell Sci.121(Pt 10), 1661–1670 (2008).
  • Lijnen HR. Matrix metalloproteinases and cellular fibrinolytic activity. Biochemistry67(1), 92–98 (2002).
  • Lijnen HR. Pleiotropic functions of plasminogen activator inhibitor-1. J. Thromb. Haemost.3(1), 35–45 (2005).
  • Jag UR, Zavadil J, Stanley FM. Insulin acts through FOXO3A to activate transcription of plasminogen activator inhibitor type 1. Mol. Endocrinol.23(10), 1587–1602 (2009).
  • Smith LH, Coats SR, Qin H et al. Differential and opposing regulation of PAI-1 promoter activity by estrogen receptor a and estrogen receptor b in endothelial cells. Circ. Res.95(3), 269–275 (2004).
  • Bastard JP, Pieroni L, Hainque B. Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance. Diabetes Metab. Res. Rev.16(3), 192–201 (2000).
  • Norata GD, Banfi C, Pirillo A et al. Oxidised-HDL3 induces the expression of PAI-1 in human endothelial cells. Role of p38 MAPK activation and mRNA stabilization. Br. J. Haematol.127(1), 97–104 (2004).
  • Macfelda K, Weiss TW, Kaun C et al. Plasminogen activator inhibitor 1 expression is regulated by the inflammatory mediators interleukin-1α, tumor necrosis factor-α, transforming growth factor-β and oncostatin M in human cardiac myocytes. J. Mol. Cell. Cardiol.34(12), 1681–1691 (2002).
  • Chen YQ, Sloan-Lancaster J, Berg DT, Richardson MA, Grinnell B, Tseng-Crank J. Differential mechanisms of plasminogen activator inhibitor-1 gene activation by transforming growth factor-β and tumor necrosis factor-α in endothelial cells. Thromb. Haemost.86(6), 1563–1572 (2001).
  • Chen HC, Feener EP. Mek1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation. Blood103(7), 2636–2644 (2004).
  • Liu RM. Oxidative stress, plasminogen activator inhibitor 1, and lung fibrosis. Antioxid. Redox Signal.10(2), 303–319 (2008).
  • Yamauchi K, Nishimura Y, Shigematsu S et al. Vascular endothelial cell growth factor attenuates actions of transforming growth factor-β in human endothelial cells. J. Biol. Chem.279(53), 55104–55108 (2004).
  • Kaneko T, Fujii S, Matsumoto A et al. Induction of plasminogen activator inhibitor-1 in endothelial cells by basic fibroblast growth factor and its modulation by fibric acid. Arterioscler. Thromb. Vasc. Biol.22(5), 855–860 (2002).
  • Keates AC, Tummala S, Peek RM Jr et al.Helicobacter pylori infection stimulates plasminogen activator inhibitor 1 production by gastric epithelial cells. Infect. Immun.76(9), 3992–3999 (2008).
  • Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell. Mol. Life Sci.57(1), 25–40 (2000).
  • Stratikos E, Gettins PG. Formation of the covalent serpin-proteinase complex involves translocation of the proteinase by more than 70 Å and full insertion of the reactive center loop into β-sheet A. Proc. Natl Acad. Sci. USA96(9), 4808–4813 (1999).
  • Dupont DM, Madsen JB, Kristensen T et al. Biochemical properties of plasminogen activator inhibitor-1. Front. Biosci.14, 1337–1361 (2009).
  • Schroeck F, Arroyo De Prada N, Sperl S, Schmitt M, Viktor M. Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (VN): mapping the binding sites on PAI-1 and VN. Biol. Chem.383(7–8), 1143–1149 (2002).
  • Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ. How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration. Nat. Struct. Biol.10(7), 541–544 (2003).
  • Deng G, Curriden SA, Hu G, Czekay RP, Loskutoff DJ. Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the somatomedin B domain of vitronectin. J. Cell. Physiol.189(1), 23–33 (2001).
  • Czekay RP, Loskutoff DJ. Plasminogen activator inhibitors regulate cell adhesion through a uPAR-dependent mechanism. J. Cell. Physiol.220(3), 655–663 (2009).
  • Durand MK, Bodker JS, Christensen A et al. Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis. Thromb. Haemost.91(3), 438–449 (2004).
  • Czekay RP, Loskutoff DJ. Unexpected role of plasminogen activator inhibitor 1 in cell adhesion and detachment. Exp. Biol. Med.229(11), 1090–1096 (2004).
  • Degryse B, Neels JG, Czekay RP, Aertgeerts K, Kamikubo Y, Loskutoff DJ. The low density lipoprotein receptor-related protein is a motogenic receptor for plasminogen activator inhibitor-1. J. Biol. Chem.279(21), 22595–22604 (2004).
  • Milliat F, Sabourin JC, Tarlet G et al. Essential role of plasminogen activator inhibitor type-1 in radiation enteropathy. Am. J. Pathol.172(3), 691–701 (2008).
  • Janicke F, Pache L, Schmitt M et al. Both the cytosols and detergent extracts of breast cancer tissues are suited to evaluate the prognostic impact of the urokinase-type plasminogen activator and its inhibitor, plasminogen activator inhibitor type 1. Cancer Res.54(10), 2527–2530 (1994).
  • Thomssen C, Harbeck N, Dittmer J et al. Feasibility of measuring the prognostic factors uPA and PAI-1 in core needle biopsy breast cancer specimens. J. Natl Cancer Inst.101(14), 1028–1029 (2009).
  • Schmitt M, Sturmheit AS, Welk A, Schnelldorfer C, Harbeck N. Procedures for the quantitative protein determination of urokinase and its inhibitor, PAI-1, in human breast cancer tissue extracts by ELISA. Methods Mol. Med.120, 245–265 (2006).
  • Schmitt M, Mengele K, Schueren E et al. European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue-associated biomarkers. Eur. J. Cancer43, 835–844 (2007).
  • Annecke K, Schmitt M, Euler U et al. uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv. Clin. Chem.45, 31–45 (2008).
  • Harbeck N, Schmitt M, Vetter M et al. Prospective biomarker trials Chemo N0 and NNBC-3 Europe validate the clinical utility of invasion markers uPA and PAI-1 in node-negative breast cancer. Breast Care3(Suppl. 2), 11–15 (2008).
  • Look MP, van Putten WL, Duffy MJ et al. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J. Natl Cancer Inst.94(2), 116–128 (2002).
  • Jänicke F, Schmitt M, Hafter R et al. The urokinase-type plasminogen activator (u-PA) is a potent predictor of early relapse in breast cancer. Fibrinolysis4, 69–78 (1990).
  • Reilly D, Christensen L, Duch M, Nolan N, Duffy MJ, Andreasen PA. Type-1 plasminogen activator inhibitor in human breast carcinomas. Int. J. Cancer50, 208–214 (1992).
  • Schmitt M, Mengele K, Gkazepis A et al. Assessment of uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 in breast cancer tissue. Historical aspects and future prospects. Breast Care3(Suppl. 2), 3–10 (2008).
  • Becker KF, Schott C, Hipp S et al. Quantitative protein analysis from formalin-fixed tissues: implications for translational clinical research and nanoscale molecular diagnosis. J. Pathol.211, 370–378 (2007).
  • Biermann JC, Holzscheiter L, Kotzsch M et al. Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumour tissue of breast cancer patients: comparison to antigen quantification by ELISA. Int. J. Mol. Med.21, 251–259 (2008).
  • Leissner P, Verjat T, Bachelot T et al. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer. BMC Cancer6, 216 (2006).
  • Lamy PJ, Verjat T, Servanton AC, Paye M, Leissner P, Mougin B. Urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA assessment in breast cancer by means of NASBA. Correlation with protein expression. Am. J. Clin. Pathol.128, 404–413 (2007).
  • Esteller M. Epigenetics in cancer. N. Engl. J. Med.358, 1148–1159 (2008).
  • Pakneshan P, Tetu B, Rabbani SA. Demethylation of urokinase promoter as a prognostic marker in patients with breast carcinoma. Clin. Cancer Res.10, 3035–3041 (2004).
  • Pulukuri SM, Estes N, Patel J, Rao JS. Demethylation-linked activation of urokinase plasminogen activator is involved in progression of prostate cancer. Cancer Res.67(3), 930–939 (2007).
  • Gao S, Nielsen BS, Krogdahl A et al. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa. Genes Chromosomes Cancer49(6), 526–538 (2010).
  • Koshelnick Y, Ehart M, Stockinger H, Binder BR. Mechanisms of signaling through urokinase receptor and the cellular response. Thromb. Haemost.82(2), 305–311 (1999).
  • Cale JM, Lawrence DA. Structure–function relationships of plasminogen activator inhibitor-1 and its potential as a therapeutic agent. Curr. Drug Targets8(9), 971–981 (2007).
  • Stefansson S, McMahon GA, Petitclerc E, Lawrence DA. Plasminogen activator inhibitor-1 in tumor growth, angiogenesis and vascular remodeling. Curr. Pharm. Des.9(19), 1545–1564 (2003).
  • Nykjaer A, Christensen EI, Vorum H et al. Mannose 6-phosphate/insulin-like growth factor-II receptor targets the urokinase receptor to lysosomes via a novel binding interaction. J. Cell. Biol.141(3), 815–828 (1998).
  • Cortese K, Sahores M, Madsen CD, Tacchetti C, Blasi F. Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR. PLoS ONE3(11), e3730 (2008).
  • Lomholt AF, Christensen IJ, Høyer-Hansen G, Nielsen HJ. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients. Acta Oncologica49(6), 805–811 (2010).
  • Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis. Markers27(3), 157–172 (2009).
  • Bifulco K, Longanesi-Cattani I, Gargiulo L et al. A urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor. FEBS Lett.582(7), 1141–1146 (2008).
  • Resnati M, Pallavicini I, Daverio R, Sidenius N, Bonini P, Blasi F. Specific immunofluorimetric assay detecting the chemotactic epitope of the urokinase receptor (uPAR). J. Immunol. Methods308(1–2), 192–202 (2006).
  • Gargiulo L, Longanesi-Cattani I, Bifulco K et al. Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor-derived SRSRY peptide. J. Biol. Chem.280(26), 25225–25232 (2005).
  • Beaufort N, Debela M, Creutzburg S et al. Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR). Biol. Chem.387(2), 217–222 (2006).
  • Beaufort N, Leduc D, Eguchi H et al. The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions. Am. J. Physiol. Lung Cell. Mol. Physiol.292(5), L1263–L1272 (2007).
  • Leduc D, Beaufort N, de Bentzmann S et al. The Pseudomonas aeruginosa LasB metalloproteinase regulates the human urokinase-type plasminogen activator receptor through domain-specific endoproteolysis. Infect. Immun.75(8), 3848–3858 (2007).
  • Schmitt M, Mengele K, Napieralski R et al. Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1. Expert Rev. Mol. Diagn. (2010) (In press).
  • Nielsen BS, Rank F, Illemann M, Lund LR, Dano K. Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor. Int. J. Cancer120(10), 2086–2095 (2007).
  • Janicke F, Schmitt M, Pache L et al. Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res. Treat.24(3), 195–208 (1993).
  • Carriero MV, Franco P, del Vecchio S et al. Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies. Cancer Res.54(20), 5445–5454 (1994).
  • Nielsen BS, Sehested M, Timshel S, Pyke C, Dano K. Messenger RNA for urokinase plasminogen activator is expressed in myofibroblasts adjacent to cancer cells in human breast cancer. Lab. Invest.74(1), 168–177 (1996).
  • Umeda T, Eguchi Y, Okino K, Kodama M, Hattori T. Cellular localization of urokinase-type plasminogen activator, its inhibitors, and their mRNAs in breast cancer tissues. J. Pathol.183(4), 388–397 (1997).
  • Dublin E, Hanby A, Patel NK, Liebman R, Barnes D. Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology. Am. J. Pathol.157(4), 1219–1227 (2000).
  • 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.163(5), 1887–1899 (2003).
  • Castello R, Landete JM, Espana F et al. Expression of plasminogen activator inhibitors type 1 and type 3 and urokinase plasminogen activator protein and mRNA in breast cancer. Thromb. Res.120(5), 753–762 (2007).
  • Hurd TC, Sait S, Kohga S et al. Plasminogen activator system localization in 60 cases of ductal carcinoma in situ.Ann. Surg. Oncol.14(11), 3117–3124 (2007).
  • Hildenbrand R, Schaaf A. The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion. Int. J. Oncol.34(1), 15–23 (2009).
  • Wang L, Madigan MC, Chen H et al. Expression of urokinase plasminogen activator and its receptor in advanced epithelial ovarian cancer patients. Gynecol. Oncol.114(2), 265–272 (2009).
  • Chen H, Hao J, Wang L, Li Y. Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression. Br. J. Cancer101(3), 432–440 (2009).
  • Chambers SK, Gertz RE Jr, Ivins CM, Kacinski BM. The significance of urokinase- type plasminogen activator, its inhibitors, and its receptor in ascites of patients with epithelial ovarian cancer. Cancer75(7), 1627–1633 (1995).
  • Boss EA, Massuger LF, Thomas CM et al. Clinical value of components of the plasminogen activation system in ovarian cyst fluid. Anticancer Res.22(1A), 275–282 (2002).
  • Hoffmann G, Pollow K, Weikel W et al. Urokinase and plasminogen activator-inhibitor (PAI-1) status in primary ovarian carcinomas and ovarian metastases compared to benign ovarian tumors as a function of histopathological parameters. Clin. Chem. Lab. Med.37(1), 47–54 (1999).
  • Koensgen D, Mustea A, Denkert C, Sun PM, Lichtenegger W, Sehouli J. Overexpression of the plasminogen activator inhibitor type-1 in epithelial ovarian cancer. Anticancer Res.26(2C), 1683–1689 (2006).
  • Schmalfeldt B, Kuhn W, Reuning U et al. Primary tumor and metastasis in ovarian cancer differ in their content of urokinase-type plasminogen activator, its receptor, and inhibitors types 1 and 2. Cancer Res.55(18), 3958–3963 (1995).
  • Ho CH, Yuan CC, Liu SM. Diagnostic and prognostic values of plasma levels of fibrinolytic markers in ovarian cancer. Gynecol. Oncol.75(3), 397–400 (1999).
  • Schmalfeldt B, Prechtel D, Harting K et al. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin. Cancer Res.7(8), 2396–2404 (2001).
  • Gleeson NC, Gonsalves R, Bonnar J. Plasminogen activator inhibitors in endometrial adenocarcinoma. Cancer72(5), 1670–1672 (1993).
  • Sandberg T, Eriksson P, Gustavsson B, Casslen B. Differential regulation of the plasminogen activator inhibitor-1 (PAI-1) gene expression by growth factors and progesterone in human endometrial stromal cells. Mol. Hum. Reprod.3(9), 781–787 (1997).
  • Osmak M, Babic D, Abramic M, Milicic D, Vrhovec I, Skrk J. Plasminogen activator inhibitor type 2: potential prognostic factor for endometrial carcinomas. Neoplasma48(6), 462–467 (2001).
  • Kobayashi H, Fujishiro S, Terao T. Impact of urokinase-type plasminogen activator and its inhibitor type 1 on prognosis in cervical cancer of the uterus. Cancer Res.54(24), 6539–6548 (1994).
  • Daneri-Navarro A, Macias-Lopez G, Oceguera-Villanueva A et al. Urokinase-type plasminogen activator and plasminogen activator inhibitors (PAI-1 and PAI-2) in extracts of invasive cervical carcinoma and precursor lesions. Eur. J. Cancer34(4), 566–569 (1998).
  • Cozzi PJ, Wang J, Delprado W et al. Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer. Hum. Pathol.37(11), 1442–1451 (2006).
  • Kumano M, Miyake H, Muramaki M, Furukawa J, Takenaka A, Fujisawa M. Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol. Oncol.27(2), 180–186 (2009).
  • Ohta S, Fuse H, Fujiuchi Y, Nagakawa O, Furuya Y. Clinical significance of expression of urokinase-type plasminogen activator in patients with prostate cancer. Anticancer Res.23(3C), 2945–2950 (2003).
  • Gupta A, Lotan Y, Ashfaq R et al. Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. Eur. Urol.55(5), 1124–1133 (2009).
  • Shariat SF, Roehrborn CG, McConnell JD et al. Association of the circulating levels of the urokinase system of plasminogen activation with the presence of prostate cancer and invasion, progression, and metastasis. J. Clin. Oncol.25(4), 349–355 (2007).
  • 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. Cancer113(6), 870–880 (2005).
  • van Veldhuizen PJ, Sadasivan R, Cherian R, Wyatt A. Urokinase-type plasminogen activator expression in human prostate carcinomas. Am. J. Med. Sci.312(1), 8–11 (1996).
  • Miyake H, Hara I, Yamanaka K, Gohji K, Arakawa S, Kamidono S. Elevation of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer. Prostate39(2), 123–129 (1999).
  • Morrissey C, True LD, Roudier MP et al. Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clin. Exp. Metastasis25(4), 377–388 (2008).
  • Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K. Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer78(3), 487–492 (1996).
  • Hofmann R, Lehmer A, Hartung R, Robrecht C, Buresch M, Grothe F. Prognostic value of urokinase plasminogen activator and plasminogen activator inhibitor-1 in renal cell cancer. J. Urol.155(3), 858–862 (1996).
  • Bhuvarahamurthy V, Schroeder J, Kristiansen G et al. Differential gene expression of urokinase-type plasminogen activator and its receptor in human renal cell carcinoma. Oncol. Rep.14(3), 777–782 (2005).
  • Ohba K, Miyata Y, Kanda S, Koga S, Hayashi T, Kanetake H. Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: correlation with tumor associated macrophage and prognosis. J. Urol.174(2), 461–465 (2005).
  • Nakanishi K, Kawai T, Torikata C, Aurues T, Ikeda T. Urokinase-type plasminogen activator, its inhibitor, and its receptor in patients with upper urinary tract carcinoma. Cancer82(4), 724–732 (1998).
  • Span PN, Witjes JA, Grebenchtchikov N et al. Components of the plasminogen activator system and their complexes in renal cell and bladder cancer: comparison between normal and matched cancerous tissues. BJU Int.102(2), 177–182 (2008).
  • Shariat SF, Monoski MA, Andrews B, Wheeler TM, Lerner SP, Slawin KM. Association of plasma urokinase-type plasminogen activator and its receptor with clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder. Urology61(5), 1053–1058 (2003).
  • Bhuvarahamurthy V, Schroeder J, Denkert C et al.In situ gene expression of urokinase-type plasminogen activator and its receptor in transitional cell carcinoma of the human bladder. Oncol. Rep.12(4), 909–913 (2004).
  • Skelly MM, Troy A, Duffy MJ et al. Urokinase-type plasminogen activator in colorectal cancer: relationship with clinicopathological features and patient outcome. Clin. Cancer Res.3(10), 1837–1840 (1997).
  • Herszenyi L, Plebani M, Carraro P et al. The role of cysteine and serine proteases in colorectal carcinoma. Cancer86(7), 1135–1142 (1999).
  • Papadopoulou S, Scorilas A, Yotis J et al. Significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) expression in human colorectal carcinomas. Tumour Biol.23(3), 170–178 (2002).
  • Seetoo DQ, Crowe PJ, Russell PJ, Yang JL. Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J. Surg. Oncol.82(3), 184–193 (2003).
  • Minoo P, Baker K, Baumhoer D, Terracciano L, Lugli A, Zlobec I. Urokinase-type plasminogen activator is a marker of aggressive phenotype and an independent prognostic factor in mismatch repair-proficient colorectal cancer. Hum. Pathol.41(1), 70–78 (2010).
  • Zlobec I, Holler S, Tornillo L, Terracciano L, Lugli A. Combined histomorphologic and immunohistochemical phenotype to predict the presence of vascular invasion in colon cancer. Dis. Colon Rectum52(6), 1114–1121 (2009).
  • Pyke C, Kristensen P, Ralfkiaer E et al. Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am. J. Pathol.138(5), 1059–1067 (1991).
  • Sato T, Nishimura G, Yonemura Y et al. Association of immunohistochemical detection of urokinase-type plasminogen activator with metastasis and prognosis in colorectal cancer. Oncology52(4), 347–352 (1995).
  • Illemann M, Bird N, Majeed A et al. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases. Int. J. Cancer124(8), 1860–1870 (2009).
  • Nekarda H, Schmitt M, Ulm K et al. Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer. Cancer Res.54(11), 2900–2907 (1994).
  • Kaneko T, Konno H, Baba M, Tanaka T, Nakamura S. Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci.94(1), 43–49 (2003).
  • Beyer BC, 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. Cancer106(5), 1026–1035 (2006).
  • Heiss MM, Babic R, Allgayer H et al. Tumor-associated proteolysis and prognosis: new functional risk factors in gastric cancer defined by the urokinase-type plasminogen activator system. J. Clin. Oncol.13(8), 2084–2093 (1995).
  • Plebani M, Herszenyi L, Carraro P et al. Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role. Clin. Exp. Metastasis15(4), 418–425 (1997).
  • Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. c-erbb-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J. Clin. Oncol.18(11), 2201–2209 (2000).
  • Kushlinskii NE, Delektorskaya VV, Mochal’nikova VV et al. Analysis of NM23 protein and components of plasminogen activation system in tumors of patients with stomach cancer with consideration for disease clinical picture and morphology. Bull. Exp. Biol. Med.146(6), 786–790 (2008).
  • Wang SN, Miyauchi M, Koshikawa N et al. Antigen expression associated with lymph node metastasis in gastric adenocarcinomas. Pathol. Int.44(12), 844–849 (1994).
  • Plebani M, Herszenyi L, Cardin R et al. Cysteine and serine proteases in gastric cancer. Cancer76(3), 367–375 (1995).
  • Nekarda H, Schlegel P, Schmitt M et al. Strong prognostic impact of tumor-associated urokinase-type plasminogen activator in completely resected adenocarcinoma of the esophagus. Clin. Cancer Res.4(7), 1755–1763 (1998).
  • Shiomi H, Eguchi Y, Tani T, Kodama M, Hattori T. Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma. Am. J. Pathol.156(2), 567–575 (2000).
  • Goscinski MA, Suo Z, Florenes VA, Vlatkovic L, Nesland JM, Giercksky KE. FAP-α and uPA show different expression patterns in premalignant and malignant esophageal lesions. Ultrastruct. Pathol.32(3), 89–96 (2008).
  • Nomiya T, Nemoto K, Miyachi H et al. Significance of plasminogen-activation system in the formation of macroscopic types and invasion in esophageal carcinoma. Anticancer Res.22(5), 2913–2916 (2002).
  • Tang Wh, Friess H, Kekis PB et al. Serine proteinase activation in esophageal cancer. Anticancer Res.21(4A), 2249–2258 (2001).
  • Torzewski M, Sarbia M, Verreet P et al. Prognostic significance of urokinase-type plasminogen activator expression in squamous cell carcinomas of the esophagus. Clin. Cancer Res.3(12 Pt 1), 2263–2268 (1997).
  • Sakakibara T, Hibi K, Koike M et al. PAI-1 expression levels in esophageal and colorectal cancers are closely correlated to those in corresponding normal tissues. Anticancer Res.26(6B), 4343–4347 (2006).
  • Goscinski MA, Suo ZH, Nesland JM et al. Seprase, dipeptidyl peptidase IV and urokinase-type plasminogen activator expression in dysplasia and invasive squamous cell carcinoma of the esophagus. A study of 229 cases from Anyang Tumor Hospital, Henan Province, China. Oncology75(1–2), 49–59 (2008).
  • Cantero D, Friess H, Deflorin J et al. Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br. J. Cancer75(3), 388–395 (1997).
  • Warnecke-Eberz U, Prenzel Kl, Baldus SE et al. Significant down-regulation of the plasminogen activator inhibitor 1 mRNA in pancreatic cancer. Pancreas36(2), 173–177 (2008).
  • Takeuchi Y, Nakao A, Harada A, Nonami T, Fukatsu T, Takagi H. Expression of plasminogen activators and their inhibitors in human pancreatic carcinoma: immunohistochemical study. Am. J. Gastroenterol.88(11), 1928–1933 (1993).
  • Harvey SR, Hurd TC, Markus G et al. Evaluation of urinary plasminogen activator, its receptor, matrix metalloproteinase-9, and von Willebrand factor in pancreatic cancer. Clin. Cancer Res.9(13), 4935–4943 (2003).
  • Nielsen A, Scarlett CJ, Samra JS et al. Significant overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma using real-time quantitative reverse transcription polymerase chain reaction. J. Gastroenterol. Hepatol.20(2), 256–263 (2005).
  • Zhou L, Hayashi Y, Itoh T, Wang W, Rui J, Itoh H. Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 and -2 in hepatocellular carcinoma. Pathol. Int.50(5), 392–397 (2000).
  • de Petro G, Tavian D, Copeta A, Portolani N, Giulini SM, Barlati S. Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and tissue-type PA messenger RNAs in human hepatocellular carcinoma. Cancer Res.58(10), 2234–2239 (1998).
  • Tavian D, de Petro G, Benetti A, Portolani N, Giulini SM, Barlati S. u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor mRNA is down-regulated in human hepatocellular carcinoma. Int. J. Cancer87(5), 644–649 (2000).
  • Zheng Q, Tang Zy, Xue Q, Shi DR, Song HY, Tang HB. Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor. J. Cancer Res. Clin. Oncol.126(11), 641–646 (2000).
  • Zhou Q, Liang LJ, Peng BG, Zhen YY. Expression and clinical significance of coagulate and fibrolysis factors in tissue and plasma from hepatocellular carcinoma patients. J. Cancer25(11), 1433–1438 (2006).
  • Dubuisson L, Monvoisin A, Nielsen BS, Le Bail B, Bioulac-Sage P, Rosenbaum J. Expression and cellular localization of the urokinase-type plasminogen activator and its receptor in human hepatocellular carcinoma. J. Pathol.190(2), 190–195 (2000).
  • Strojan P, Budihna M, Smid L, Vrhovec I, Skrk J. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in tissue and serum of head and neck squamous cell carcinoma patients. Eur. J. Cancer34(8), 1193–1197 (1998).
  • Strojan P, Budihna M, Smid L, Vrhovec I, Skrk J. Urokinase-type plasminogen activator, plasminogen activator inhibitor type 1 and cathepsin D. Analysis of their prognostic significance in squamous cell carcinoma of the head and neck. Anticancer Res.20(5C), 3975–3981 (2000).
  • Speleman L, Kerrebijn JD, Look MP, Meeuwis CA, Foekens JA, Berns EM. Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma. Head Neck29(4), 341–350 (2007).
  • Naka T, Kuester D, Boltze C et al. Expression of matrix metalloproteinases-1, -2, and -9; tissue inhibitors of matrix metalloproteinases-1 and -2; cathepsin B; urokinase plasminogen activator; and plasminogen activator inhibitor, type I in skull base chordoma. Hum. Pathol.39(2), 217–223 (2008).
  • Shi Z, Stack MS. Urinary-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of the oral cavity. Biochem. J.407(2), 153–159 (2007).
  • Baker EA, Leaper DJ, Hayter JP, Dickenson AJ. Plasminogen activator system in oral squamous cell carcinoma. Br. J. Oral Maxillofac. Surg.45(8), 623–627 (2007).
  • Nozaki S, Endo Y, Kawashiri S et al. Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity: association with mode of invasion and lymph node metastasis. Oral Oncol.34(1), 58–62 (1998).
  • Nagata M, Fujita H, Ida H et al. Identification of potential biomarkers of lymph node metastasis in oral squamous cell carcinoma by cDNA microarray analysis. Int. J. Cancer106(5), 683–689 (2003).
  • 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. Craniomaxillofac. Surg.33(3), 191–196 (2005).
  • Hundsdorfer B, Zeilhofer HF, Bock KP, Dettmar P, Schmitt M, Horch HH. Comparison of urokinase type plasminogen activators (uPA) and plasminogen activator inhibitors (PAI-1) in primary resection of oral squamous cell carcinoma. Mund Kiefer Gesichtschirurgie8(3), 180–190 (2004).
  • Bindal AK, Hammoud M, Shi WM, Wu SZ, Sawaya R, Rao JS. Prognostic significance of proteolytic enzymes in human brain tumors. J. Neurooncol.22(2), 101–110 (1994).
  • Caccamo DV, Keohane ME, McKeever PE. Plasminogen activators and inhibitors in gliomas: an immunohistochemical study. Mod. Pathol.7(1), 99–104 (1994).
  • Landau BJ, Kwaan HC, Verrusio EN, Brem SS. Elevated levels of urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 in malignant human brain tumors. Cancer Res.54(4), 1105–1108 (1994).
  • Arai Y, Kubota T, Nakagawa T, Kabuto M, Sato K, Kobayashi H. Production of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) in human brain tumours. Acta Neurochirurgica140(4), 377–385 (1998).
  • Levicar N, Nuttall RK, Lah TT. Proteases in brain tumour progression. Acta Neurochirurgica145(9), 825–838 (2003).
  • Salmaggi A, Croci D, Prina P et al. Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma. Cancer Biol. Ther.5(2), 204–209 (2006).
  • Kono S, Rao JS, Bruner JM, Sawaya R. Immunohistochemical localization of plasminogen activator inhibitor type 1 in human brain tumors. J. Neuropathol. Exp. Neurol.53(3), 256–262 (1994).
  • Sandstrom M, Johansson M, Sandstrom J, Bergenheim AT, Henriksson R. Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression. Int. J. Dev. Neurosci.17(5–6), 473–481 (1999).
  • Hsu DW, Efird JT, Hedley-Whyte ET. Prognostic role of urokinase-type plasminogen activator in human gliomas. Am. J. Pathol.147(1), 114–123 (1995).
  • Iwadate Y, Hayama M, Adachi A et al. High serum level of plasminogen activator inhibitor-1 predicts histological grade of intracerebral gliomas. Anticancer Res.28(1B), 415–418 (2008).
  • Yamamoto M, Sawaya R, Mohanam S et al. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo.Cancer Res.54(14), 3656–3661 (1994).
  • Zhang X, Bu XY, Zhen HN, Fei Z, Zhang JN, Fu LA. Expression and localisation of urokinase-type plasminogen activator gene in gliomas. J. Clin. Neurosci.7(2), 116–119 (2000).
  • Chu QD, Hurd TC, Harvey S et al. Overexpression of urinary plasminogen activator (uPA) protein and mRNA in thyroid carcinogenesis. Diagn. Mol. Pathol.13(4), 241–246 (2004).
  • Horvatic Herceg G, Herceg D, Kralik M, Bence-Zigman Z, Tomic-Brzac H, Kulic A. Urokinase-type plasminogen activator and its inhibitor in thyroid neoplasms: a cytosol study. Wiener Klinische Wochenschrift118(19–20), 601–609 (2006).
  • Ulisse S, Baldini E, Toller M et al. Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas. Eur. J. Cancer42(15), 2631–2638 (2006).
  • Stabuc B, Markovic J, Bartenjev I, Vrhovec I, Medved U, Kocijancic B. Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma. Oncol. Rep.10(3), 635–639 (2003).
  • de Vries TJ, Mooy CM, van Balken MR et al. Components of the plasminogen activation system in uveal melanoma – a clinico-pathological study. J. Pathol.175(1), 59–67 (1995).
  • Gershtein ES, Medvedeva SV, Babkina IV, Kushlinskii NE, Trapeznikov NN. Tissue- and urokinase-type plasminogen activators and type 1 plasminogen activator inhibitor in melanomas and benign skin pigment neoplasms. Bull. Exp. Biol. Med.132(1), 670–674 (2001).
  • Hanekom GS, Stubbings HM, Kidson SH. The active fraction of plasmatic plasminogen activator inhibitor type 1 as a possible indicator of increased risk for metastatic melanoma. Cancer Detect. Prevent.26(1), 50–59 (2002).
  • Ito Y, Takeda T, Kobayashi T et al. Plasminogen activation system in active even in thyroid tumors; an immunohistochemical study. Anticancer Res.16(1), 81–89 (1996).
  • Kushlinskii NE, Gershtein ES, Kazantseva IA et al. [Plasminogen activators of urokinase and tissue types and their inhibitor (PAI-1) in cytosol fraction in thyroid diseases]. Vestn. Akad. Med. Nauk SSSR(5), 32–34 (2001).
  • Choong PF, Ferno M, Akerman M et al. Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas. Int. J. Cancer69(4), 268–272 (1996).
  • Benassi MS, Ponticelli F, Azzoni E et al. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas. Histol. Histopathol.22(9), 1017–1024 (2007).
  • Kushlinskii NE, Yusifov AI, Gershtein ES, Solov’ev YN, Trapeznikov NN. Plasminogen activators and their inhibitor in bone tumors and tumor-like damages. Bull. Exp. Biol. Med.132(2), 780–782 (2001).
  • Hakel C, Ueda Y, Tsuchya H, Herrera A, Blasius S, Roessner A. Plasminogen activators and their inhibitor in osteosarcomas and other bone tumors. Zentralblatt fuer Pathologie140(4–5), 363–369 (1994).
  • Hackel C, Czerniak B, Ayala AG, Radig K, Roessner A. Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma. Cancer79(1), 53–58 (1997).
  • Thewes M, Elsner E, Wessner D, Engst R, Ring J. The urokinase plasminogen activator system in angiosarcoma, Kaposi’s sarcoma, granuloma pyogenicum, and angioma: an immunohistochemical study. Int. J. Dermatol.39(3), 188–191 (2000).
  • Morii T, Yabe H, Morioka H, Yamada R, Nakagawa T, Toyama Y. Prognostic relevance of urokinase type plasminogen activator, its receptor and inhibitors in chondrosarcoma. Anticancer Res.20(5A), 3031–3036 (2000).
  • Taubert H, Wurl P, Greither T et al. Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients. Br. J. Cancer102(4), 731–737 (2010).
  • Oka T, Ishida T, Nishino T, Sugimachi K. Immunohistochemical evidence of urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma. Cancer Res.51(13), 3522–3525 (1991).
  • Hofmann HS, Bartling B, Simm A et al. Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human 59.620-element oligonucleotide array. Oncol. Rep.16(3), 587–595 (2006).
  • Volm M, Mattern J, Koomagi R. Relationship of urokinase and urokinase receptor in non-small cell lung cancer to proliferation, angiogenesis, metastasis and patient survival. Oncol. Rep.6(3), 611–615 (1999).
  • Salden M, Splinter TA, Peters HA et al. The urokinase-type plasminogen activator system in resected non-small-cell lung cancer. Rotterdam Oncology Thoracic Study Group. Ann. Oncol.11(3), 327–332 (2000).
  • 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.54(17), 4671–4675 (1994).
  • Werle B, Kotzsch M, Lah TT et al. Cathepsin B, plasminogen activator-inhibitor (PAI-1) and plasminogen activator-receptor (uPAR) are prognostic factors for patients with non-small cell lung cancer. Anticancer Res.24(6), 4147–4161 (2004).
  • Zekanowska E, Cieslinski K, Rosc D. Plasminogen activator inhibitor type 1 (PAI-1) in blood and tissue extracts of patients with non-small cell lung cancer. Pneumonologia i Alergologia Polska72(9–10), 409–414 (2004).
  • Pavey SJ, Marsh NA, Ray MJ, Butler D, Dare AJ, Hawson GA. Changes in plasminogen activator inhibitor-1 levels in non-small cell lung cancer. Boll. Soc. Ital. Biol. Sper.72(11–12), 331–340 (1996).
  • Pedersen H, Grondahl-Hansen J, Francis D et al. Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma. Cancer Res.54(1), 120–123 (1994).
  • Sgier D, Zuberbuehler K, Pfaffen S, Neri D. Isolation and characterization of an inhibitory human monoclonal antibody specific to the urokinase-type plasminogen activator, uPA. Protein Eng. Des. Sel.23(4), 261–269 (2010).

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