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Biological and Clinical Relevance of the Tumor-Associated Serine Protease uPA

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Molecular Diagnostics of Cancer

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Abstract

Two types of serine proteases, uPA (urokinase-type plasminogen activator) and tPA (tissue-type plasminogen activator), are known to convert plasminogen into plasmin [1]. tPA is mainly involved in intravascular thrombolysis [1,2] whereas uPA mediates pericellular proteolysis during cell migration and tissue remodeling under physiological and pathophysiological conditions [2, 3]. Although initially secreted in the form of an enzymatically inactive, single-chain proenzyme (pro-uPA), uPA exerts its proteolytic function on normal cells and tumor cells as an ectoenzyme after having bound to a specific high-affinity cell surface receptor (uPA-R) [4–6]. uPA-R on cells seems to be the reaction site for uPA-mediated plasminogen activation, also in solid tumors. Quantitative assessments of tumor tissues, invasion assays with tumor explants in experimental animals and in vitro investigations with tumor cells suggest that tumor invasion and metastasis are correlated with elevated levels of uPA and the presence of the uPA-R [2–6]. Tissues of primary cancer and/or metastases of the breast, ovary, prostate, cervix uteri, bladder, lung and gastrointestinal tract have been reported to contain high amounts of uPA compared to benign control tissues [2, 3]. uPA is produced and secreted as pro-uPA by normal cells and by tumor cells [2, 3]. Pro-uPA may be converted by small amounts of serine proteases (plasmin, kallikrein, trypsin) or cathepsin B or L into the enzymatically active, high-molecular-weight, two-chain form HMW-uPA which subsequently converts plasminogen into the serine protease plasmin [7–10].

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References

  1. Bachmann F (1987) Thrombosis and haemostasis. In: Verstraete M, Lijnen HR, Arnout J (eds) International Society on Thrombosis and Haemostasis. Leuven University Press, Leuven, pp 227–265

    Google Scholar 

  2. Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 44:139–266

    Article  PubMed  CAS  Google Scholar 

  3. Markus G (1988) The relevance of plasminogen activators to neoplastic growth. Enzyme 40:158–172

    PubMed  CAS  Google Scholar 

  4. Blasi F, Stoppelli MP, Cubellis V (1986) The receptor for urokinase-plasminogen activator. J Cell Biochem 32:179–186

    Article  PubMed  CAS  Google Scholar 

  5. Blasi F (1988) A surface receptor for urokinase plasminogen activator: a link between the cytoskeleton and the extracellular matrix. Protoplasma 145, 95–98

    Article  Google Scholar 

  6. Blasi F (1988) Surface receptors for urokinase plasminogen activator. Fibrinolysis 2:73–84

    Article  CAS  Google Scholar 

  7. Kobayashi H, Schmitt M, Goretzki L, Chucholowski N, Calvete J, Kramer M, Giinzler WA, Janicke F, Graeff H (1990) Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (pro-uPA). J Biol Chem 266:5147–5152

    Google Scholar 

  8. Ichinose A, Fujikawa K, Suyama T (1986) The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 261:3486–3489

    PubMed  CAS  Google Scholar 

  9. Schmitt M, Kanayama N, Henschen A, Hollrieder A, Hafter R, Gulba D, Janicke F, Graeff H (1989) Elastase released from human granulocytes stimulated with N-formyl-chemotactic peptide prevents activation of tumor cell prourokinase. FEBS Lett 255:83–88

    Article  PubMed  CAS  Google Scholar 

  10. Schmitt M, Goretzki L, Janicke F, Calvete J, Eulitz M, Kobayashi H, Chucholowski N, Graeff H (1991) Biological and clinical relevance of the urokinase-type plasminogen activator (uPA) in breast cancer. Biomed Biochim Acta 50:737–741

    Google Scholar 

  11. Duffy MJ, O’Grady P, Devaney D, O’Siorain L, Fennelly JJ, Lijnen HR (1988) Tissue-type plasminogen activator, a new prognostic marker in breast cancer. Cancer Res 48:1348–1349

    PubMed  CAS  Google Scholar 

  12. Roldan AL, Cubellis MV, Masucci MT, Behrendt W, Lund LR, Dano K, Appella E, Blasi F (1990) Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J 9:467–474

    PubMed  CAS  Google Scholar 

  13. Kirchheimer JC, Binder BR (1991) Function of receptor-bound urokinase. Semin Thromb Hemost 17:246–250

    Article  PubMed  CAS  Google Scholar 

  14. Appella E, Robinson EA, Ullrich SJ, Stoppelli MP, Corti A, Casani G, Blasi F (1987) The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases. J Biol Chem 262:4437–4440

    PubMed  CAS  Google Scholar 

  15. Chucholowski N, Schmitt M, Goretzki L, Schiiren E, Moniwa N, Weidle U, Kramer M, Wagner D, Janicke F, Graeff H (1992) Flow cytofluorometry in tumor cell analysis. Biochem Soc Trans 20:208–216

    PubMed  CAS  Google Scholar 

  16. Vassalli JD, Baccino D, Belin D (1985) A cellular binding site for the Mr 55 000 form of the human plasminogen activator, urokinase. J Cell Biol 100:86–92

    Article  PubMed  CAS  Google Scholar 

  17. Stoppelli MP, Tacchetti C, Cubellis MV, Corti A, Hearing VJ, Cassani G, Appella E, Blasi F (1986) Autocrine saturation of pro-urokinase receptors on human A431 cells. Cell 45:675–684

    Article  PubMed  CAS  Google Scholar 

  18. Chucholowski N, Schmitt M, Rettenberger P, Schiiren E, Moniwa N, Goretzki L, Wilhelm O, Weidle U, Janicke F and Graeff H (1992) Flow cytofluorometric analysis of the urokinase receptor (uPA-R) on tumor cells by fluorescent uPA-ligand or monoclonal antibody #3936 Fibrinolysis 6, Suppl. 4:95–102

    Google Scholar 

  19. Estreicher A, Muhlhauser J, Carpentier JL, Orci L, Vassalli JD (1990) The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. J Cell Biol 111:783–792

    Article  PubMed  CAS  Google Scholar 

  20. Kirchheimer JC, Nong YH, Remold HG (1988) IFN-gamma, tumor necrosis factor-alpha, and urokinase regulate the expression of urokinase receptors on human monocytes. J Immunol 141:4229–4234

    PubMed  CAS  Google Scholar 

  21. Stoppelli MP, Corti A, Soffientini A, Cassani G, Blasi F and Assoian RK (1985) Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes. Proc Natl Acad Sci USA 82:4939–4943

    Article  PubMed  CAS  Google Scholar 

  22. Nielsen LS, Kellermann GM, Behrendt N, Picone R, Dano K, Blasi F (1988) A 55000–60000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification. J Biol Chem 263:2358–2363

    PubMed  CAS  Google Scholar 

  23. Behrendt N, Ronne E, Ploug M, Petri T, Lober D, Nielsen LS, Schleuning WD, Blasi F, Appella E, Dano K (1990) The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants. J Biol Chem 265:6453–6460

    PubMed  CAS  Google Scholar 

  24. Ploug M, Ronne E, Behrendt N, Jensen AL, Blasi F, Dano K (1991) Cellular receptor for urokinase plasminogen activator: carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem 266:1926–1933

    PubMed  CAS  Google Scholar 

  25. Ploug M, Behrendt N, Lober D, Dano K (1991) Protein structure and membrane anchorage of the cellular receptor for urokinase-type plasminogen activator. Semin Thromb Hemost 17:183–193

    Article  PubMed  CAS  Google Scholar 

  26. Vassalli J-D, Belin D (1987) Amiloride selectively inhibits the urokinase-type plasminogen activator. FEBS Lett 214:187–191

    Article  PubMed  CAS  Google Scholar 

  27. Schneider J (1990) Interactions of saruplase with acetylsalycylic acid, heparin, glyceryl trinitrate, tranexamic acid and aprotinin in a rabbit pulmonary thrombosis model. Arzneimittelforschung 40:1180–1184

    PubMed  CAS  Google Scholar 

  28. Stephens RW, Pollanen J, Tapiovaara H, Leung KC, Sim PS, Salonen EM, Ronne E, Behrendt N, Dano K, Vaheri A (1989) Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol 108:1985–1987

    Article  Google Scholar 

  29. Schmitt M, Chucholowski N, Busch E, Hellmann D, Wagner B, Goretzki L, Janicke F, Gunzler WA, Graeff H (1991) Fluorescent probes to assess the receptor for the urokinase-type plasminogen activator on tumor cells. Sem Thromb Hemost 17:291–302

    Article  CAS  Google Scholar 

  30. Miles LA, Plow EF (1988) Plasminogen receptors: ubiquitous sites for cellular regulation of fibrinolysis. Fibrinolysis 2:61–71

    Article  CAS  Google Scholar 

  31. Lu H, Mirshahi M, Krief P, Soria C, Soria J, Mishal Z, Bertrand O, Perrot JY, Li H, Picot C (1988) Parallel induction of fibrinolysis and receptors for plasminogen and urokinase by interferon gamma on U937 cells. Biochem Biophys Res Commun 155:418–422

    Article  PubMed  CAS  Google Scholar 

  32. Appella E, Blasi F (1987) The growth factor module of urokinase is the binding sequence for its receptor. Ann NY Acad Sci 511:192–195

    Article  PubMed  CAS  Google Scholar 

  33. Spyratos F, Maudelonde T, Brouillet J-P, Brunet M, Defrenne A, Andrieu C, Hacene K, Desplaces A, Rouesse J, Rochefort H (1989) Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet 8672:1115–1118

    Article  Google Scholar 

  34. Tandon AT, Clark GM, Chamness GC, Chrigwin JM, McGuire WL (1990) Cathepsin D and prognosis in breast cancer. N Engl J Med 322:297–302

    Article  PubMed  CAS  Google Scholar 

  35. Thorpe SM, Rochefort H, Garcia M, Freiss G, Christensen IJ, Khalaf S, Paolucci F, Pau B, Rasmussen BB, Rose C (1989) Association between high concentrations of Mr 52 000 cathepsin D and poor prognosis in primary human breast cancer. Cancer Res 49:6008–6014

    PubMed  CAS  Google Scholar 

  36. Sloane BF, Dunn JR, Honn KV (1981) Lysosomal cathepsin B: correlation with metastatic potential. Science 212:1151–1153

    Article  PubMed  CAS  Google Scholar 

  37. Trygvasson K, (1989) Extracellular matrix and its enzymatic degradation in tumor invasion. In: Liotta LA (ed) Influence of tumor development on the host. Kluwer, Dordrecht, pp 72–83

    Chapter  Google Scholar 

  38. Lah TT, Buck MR, Honn KV, Crissman JD, Rao NC, Liotta LA, Sloane BF(1989)Degradation of laminin by tumor cathepsin B. Clin Exp Metastasis 7:461–468

    Article  PubMed  CAS  Google Scholar 

  39. Sloane BF, Ryan RE, Rozhin J, Lah TT, Crissman JD, Honn KV (1986) Cathepsin B: a proteinase linked to metastases. In: Proteinases in inflammation and tumor invasion, de Gruyter, Berlin, pp 93–106

    Google Scholar 

  40. Astedt B, Holmberg L (1976) Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature 261:595–597

    Article  PubMed  CAS  Google Scholar 

  41. Jänicke F, Schmitt M, Hafter R, Hollrieder A, Babic R, Ulm K, Gössner W, Graeff H (1990) The urokinase-type plasminogen activator (u-PA) is a potent predictor of early relapse in breast cancer. Fibrinolysis 4:69–78

    Article  Google Scholar 

  42. Jänicke F, Schmitt M, Graeff H (1991) Clinical relevance of the urokinase-type and tissue-type plasminogen activators and of their type 1 inhibitor in breast cancer. Semin Thromb Hemost 17:303–312

    Article  PubMed  Google Scholar 

  43. Schmitt M, Jänicke F, Hafter R, Hollrieder A, Kanayama N, Gulba D, Graeff H (1990) Tumor-associated fibrinolysis in human breast cancer: Detection and quantitation of the urokinase-type plasminogen activator (uPA) by ELISA and immunohistochemistry. In: Matsuda M, Iwanaga S, Takada A, Henschen A (eds) Fibrinogen. Current basic and clinical aspects. Elsevier, Amsterdam, pp 213–222

    Google Scholar 

  44. Jänicke F, Schmitt M, Ulm K, Gössner W, Graeff H (1989) Urokinase-type plasminogen activator antigen and early relapse in breast cancer. Lancet II 8670:1049

    Article  Google Scholar 

  45. Duffy MJ, Reilley D, O’Sullivan C, O’Higgins N, Fennelly JJ, Andreasen P (1990)Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer. Cancer Res 50:6827–6829

    PubMed  CAS  Google Scholar 

  46. Schmitt M, Jänicke F, Graeff H (1990) Tumor-associated fibrinolysis: The prognostic relevance of plasminogen activators uPA and tPA in human breast cancer. Blood Coagulation Fibrinolysis 1:695–702

    PubMed  CAS  Google Scholar 

  47. Pöllänen J, Hedman K, Nielsen LS, Dano K, Vaheri A (1988) Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol 106:87–95

    Article  PubMed  Google Scholar 

  48. Schmitt M, Jänicke F, Graeff H (1992) Tumor-associated proteases. Fibrinolysis 6, Suppl. 4:3–26

    Google Scholar 

  49. Grondahl-Hansen J, Kirkeby LT, Ralfkiaer E, Kristensen P, Lund LR, Dano K (1989) Urokinase-type plasminogen activator in endothelial cells curing acute inflammation of the appendix. Am J Pathol 135:631–636

    PubMed  CAS  Google Scholar 

  50. Grondahl-Hansen J, Ralfkiaer E, Kirkeby LT, Kristensen P, Lund LR, Dano K (1991) Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol 138:111–117

    PubMed  CAS  Google Scholar 

  51. Sier CFM, Fellbaum C, Verspaget HW, Schmitt M, Griffioen G, Graeff H, Höfler H, Lamers CB (1991) Immunolocalization of urokinase-type plasminogen activator (uPA) in adenomas and carcinomas of the human colon. Histopathology 19:231–237

    Article  PubMed  CAS  Google Scholar 

  52. Kohga S, Harvey SR, Weaver RM, Markus G (1985) Localization of plasminogen activators in human colon cancer by immunoperoxidase staining. Cancer Res 45:1787–1796

    PubMed  CAS  Google Scholar 

  53. Kohga S, Harvey SR, Suzumiya J, Sumiyoshi A, Markus G (1989) Comparison of the immunohistochemical localisation of urokinase in normal and cancerous human colon tissue. Fibrinolysis 3:17–22

    Article  Google Scholar 

  54. Kwaan C, Keer HN, Radosevich JA, Cajot JF, Ernst R (1991) Components of the plasminogen-plasmin system in human tumor cell lines. Semin Thromb Hemost 17:175–182

    Article  PubMed  CAS  Google Scholar 

  55. Nishino N, Aoki K, Tokura Y, Sakagushi S, Takada Y, Takada A (1989) The urokinase type plasminogen activator in cancer of digestive tracts. Thromb Res 50:527–535

    Article  Google Scholar 

  56. Wajima T (1991) Fibrinolytic profiles in patients with small cell carcinoma of the lung. Semin Thromb Hemost 17:280–285

    Article  PubMed  CAS  Google Scholar 

  57. Brunner G, Simon MM, Kramer MD (1990) Activation of pro-urokinase by the human T cell-associated serine proteinase HuTSP-1. FEBS Lett 260:141–144

    Article  PubMed  CAS  Google Scholar 

  58. Schlechte W, Brittain M, Boyd D (1990) Invasion of extracellular matrix by cultured colon cells: dependence on urokinase receptor display. Cancer Commun 2:173–179

    PubMed  CAS  Google Scholar 

  59. Niedballa MJ, Bajetta S, Carbone R, Satorelli AC (1990) Regulation of human squamous cell carcinoma plasma membrane associated urokinase plasminogen activator by epidermal growth factor. Cancer Commun 2:317–324

    Google Scholar 

  60. Bulletti C, Jasonni VM, Polli V, Cappuccini F, Galassi A, Flamigni C (1991) Basement membrane in human endometrium: possible role of proteolytic enzymes in developing hyperplasia and carcinoma. Ann NY Acad Sci 622: 376–382

    Article  PubMed  CAS  Google Scholar 

  61. Masucci MT, Pedersen N, Blasi F (1991) A soluble, ligand binding mutant of the human urokinase plasminogen activator receptor. J Biol Chem 266: 8655–8658

    PubMed  CAS  Google Scholar 

  62. Dini G, Fibbi G, Pasquali F, del Rosso M (1985) Plasminogen activator: morphological evidence of binding, internalization and delivery to lysosomes in 3T3 mouse fibroblasts. Histochem J 17:333–341

    Article  PubMed  CAS  Google Scholar 

  63. Pedersen N, Rönne E, Schmitt M, Dano K, Hoyer-Hansen G, Kuhn W, Jänicke F, Blasi F (1991) Presence of a water-soluble unoccupied form of the urokinase-receptor in the ascitic fluid and plasma of patients with ovarian cancer. J Clin Invest (submitted)

    Google Scholar 

  64. Fukao H, Tanaka N, Ueshima S, Okada T, Yasutomi M, Matsuo O (1991) Plasminogen activator inhibitor in stomach and colorectal carcinoma. Semin Thromb Hemost 17:276–279

    Article  PubMed  CAS  Google Scholar 

  65. Burtin P, Chavanel G, Andre-Bougaran J, Gentile A (1987) The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study. Int J Cancer 39:170–178

    Article  PubMed  CAS  Google Scholar 

  66. Clavel C, Chavanel G, Birembaut P (1986) Detection of the plasmin system In human mammary pathology using immunofluorescence. Cancer Res 46: 5743–5747

    PubMed  CAS  Google Scholar 

  67. Clavel C, Birembaut P (1988) Proteases et carcinomes mammaires. Ann Pathol 8:20–24

    PubMed  CAS  Google Scholar 

  68. Duffy M, O’Grady P, Devaney D, O’Siorain L, Fennelly JJ, Lijnen HJ (1988) Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Cancer 62:531–533

    Article  PubMed  CAS  Google Scholar 

  69. Duffy MJ, Reilly D, O’Sullivan C, O’Higgins N, Fennelly JJ (1990) Urokinase plasminogen activator and prognosis in breast cancer. Lancet 335/8681:108

    Article  PubMed  CAS  Google Scholar 

  70. O’Grady P, Lijnen HR, Duffy MJ (1985) Multiple forms of plasminogen activator in breast tumors. Cancer Res 45:6216–6218

    PubMed  Google Scholar 

  71. Duffy MJ, Brouillet JP, Reilley D, McDermott E, O’Higgins N, Fennelly JJ, Maudelonde TA, Rochefort H (1991) Cathepsin D concentration in breast cancer cytosols: correlation with biochemical, histological and clinical findings. Clin Chem 37:101–104

    PubMed  CAS  Google Scholar 

  72. Evers JL, Patel J, Madeja JM, Schneider SL, Hobika GH, Camiolo SM, Markus GB (1982) Plasminogen activator activity and composition in human breast cancer. Cancer Res 42:219–226

    PubMed  CAS  Google Scholar 

  73. Graeff H, Jänicke F, Schmitt M (1991) Klinische und prognostische Bedeutung tumorassoziierter Proteasen in der gynäkologischen Onkologie. Geburtshilfe Frauenheilkd 51:90–99

    Article  PubMed  CAS  Google Scholar 

  74. Grondahl-Hansen J, Agerlin M, Munkholm-Larsen P, Bach F, Nielsen LS, Dombernowsky P, Dano K (1988) Sensitive and specific enzyme-linked immunosorbent assay for urokinase-type plasminogen activator and its application to plasma from patients with breast cancer. J Lab Clin Invest 111:42–51

    CAS  Google Scholar 

  75. Hayashi S, Yamada K (1985) Urokinase-type plasminogen activator in ascites obtained from the patient with mammary cancer. Thromb Res 38:459–467

    Article  PubMed  CAS  Google Scholar 

  76. Layer GT, Cederholm-Williams SA, Gaffney PJ, Houlbrook S, Mahmoud M, Pattison M, Burnand K (1987) Urokinase - the enzyme responsible for invasion and metastasis in human breast carcinoma? Fibrinolysis 1:237–240

    Article  Google Scholar 

  77. Layer GT, Burnand KG, Gaffney PJ, Cederholm-Williams SA, Mahmoud M, Houlbrook S, Pattison M (1987) Tissue plasminogen activators in breast cancer. Thromb Res 45:601–607

    Article  PubMed  CAS  Google Scholar 

  78. McGregor IR, Miller WR (1988) Urokinase and tissue-type plasminogen activators are present in breast cyst fluids. Eur J Cancer Clin Oncol 24:985–989

    Article  Google Scholar 

  79. Mira-y-Lopez R, Osborne MP, DePalo AJ, Ossowski L (1991) Estradiol modulation of plasminogen activator production in organ cultures of human breast caracinomas: correlation with clinical outcome of anti-estrogen therapy. Int J Cancer 47:827–832

    Article  PubMed  CAS  Google Scholar 

  80. Needham GK, Sherbet GV, Farndon JR, Harris AL (1987) Binding of urokinase to specific receptor sites on human breast cancer membranes. Br J Cancer 55:13–16

    Article  PubMed  CAS  Google Scholar 

  81. Needham GK, Nicholson S, Angus B, Farndon JR, Harris AL (1988) Relation of membrane-bound tissue type and urokinase type plasminogen activators in human breast cancers to estrogen and epidermal growth factor receptors. Cancer Res 48:6603–6607

    PubMed  CAS  Google Scholar 

  82. Sappino AS, Busson N, Belin D, Vassalli JD (1987) Increase of urokinase-type plasminogen activator gene expression in human lung and breast carcinomas. Cancer Res 45:601–607

    Google Scholar 

  83. Sherman MR, Tuazon FB, Miller LK (1980) Estrogen receptor cleavage and plasminogen activation by enzymes in human breast tumor cytosol. Endocrinology 106:1715–1727

    Article  PubMed  CAS  Google Scholar 

  84. Tissot J-D, Hauert J, Bachmann F (1984) Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas. Int J Cancer 34:295–302

    Article  PubMed  CAS  Google Scholar 

  85. Koelbl H, Kirchheimer JC, Tatra G, Christ G, Binder BR (1988) Increased plasma levels of urokinase-type plasminogen activator with endometrial and cervical cancer. Obstet Gynecol 72:252–256

    PubMed  CAS  Google Scholar 

  86. Larsson G, Larsson A, Astedt B (1987) Tissue plasminogen activator and urokinase in normal, dysplastic and cancerous squamous epithelium of the uterine cervix. Thromb Haemost 58:822–826

    PubMed  CAS  Google Scholar 

  87. Saito K, Nagashima M, Iwata M, Hamada H, Sumiyoshi K, Takada Y, Takada A (1990) The concentration of tissue type plasminogen activator and urokinase in plasma and tissues of patients with ovarian and uterine tumors. Thromb Res 58:355–366

    Article  PubMed  CAS  Google Scholar 

  88. Burtin P, Chavanel G, André J (1985) The plasmin system in human colonic tumors: an immunofluorescence study. Int J Cancer 35:307–314

    Article  CAS  Google Scholar 

  89. De Bruin PA, Griffioen G, Verspaget HW, Verheijen JH, Lamers CB (1987) Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps and adenocarcinomas. Cancer Res 47:4654–4657

    PubMed  Google Scholar 

  90. De Bruin PA, Griffioen G, Verspaget HW, Verheijen JH, Dooijeward G, van den Ingh HF, Lamers CB (1987) Plasminogen activator profiles in neoplastic tissues of the human colon. Cancer Res 4:4520–4524

    Google Scholar 

  91. Wojtukiewicz MZ, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Rousseau SM, Stump DC (1990) Abnormal regulation of coagulation/ fibrinolysis in small cell carcinoma of the lung. Cancer 65:481–485

    Article  PubMed  CAS  Google Scholar 

  92. Harvey SR, Lawrence DD, Madeja JM, Abbey SJ, Markus G (1988) Secretion of plasminogen activators by human colorectal and gastric tumor explants. Clin Exp Metast 6:431–450

    Article  CAS  Google Scholar 

  93. Huber K, Wojta J, Kirchheimer JC, Ermler D, Binder BR (1988) Plasminogen activators and plasminogen activator inhibitor in malignant ascitic fluid. Eur J Clin Invest 18:595–599

    Article  PubMed  CAS  Google Scholar 

  94. Kirchheimer JC, Huber K, Wagner O, Binder BR (1987) Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. Br J Haematol 66: 85–89

    Article  PubMed  CAS  Google Scholar 

  95. Marian B, Harvey S, Infante D, Markus G, Winawer S, Friedman E (1990) Urokinase secretion from human colon carcinomas induced by endogenous diglycerides. Cancer Res 50:2245–2250

    PubMed  CAS  Google Scholar 

  96. Pyke C, Kristensen P, Ralfkiaer E, Grondahl-Hansen J, Eriksen J, Blasi F, Dano K (1991) 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 138:1059–1067

    PubMed  CAS  Google Scholar 

  97. Sim PS, Stephens RW, Fayle DR, Doe WF (1988) Urokinase-type plasminogen activator in colorectal carcinomas and adenomatous polyps: quantitative expression of active and proenzyme. Int J Cancer 42:483–488

    Article  PubMed  CAS  Google Scholar 

  98. Tanaka N, Fukao H, Ueshima S, Okada K, Yasutomi M, Matsuo O (1991) Plasminogen activator inhibitor 1 in human carcinoma tissues. Int J Cancer 48:481–484

    Article  PubMed  CAS  Google Scholar 

  99. Verspaget HW, Verheijen JH, de Bruin PA, Griffioen G, Lamers CB (1989) Plasminogen activators in (pre) malignant conditions of the colorectum. Eur J Cancer Clin Oncol 25:565–569

    Article  PubMed  CAS  Google Scholar 

  100. Takai S, Yamamura M, Tanaka K, Kawanishi H, Tsuji M, Nakane Y, Hioki K, Yamamoto M (1991) Plasminogen activators in human gastric cancers: correlation with DNA ploidy and immunohistochemical staining. Int J Cancer 48:20–27

    Article  PubMed  CAS  Google Scholar 

  101. Gorelik U, Lindner A, Mayer M (1990) Protease and plasminogen activity in human bladder carcinoma. Br J Urol 66:170–174

    Article  PubMed  CAS  Google Scholar 

  102. Hasui Y, Suzumiya J, Marutsuka K, Sumiyoshi A, Hashida S, Ishikawa E (1989) Comparative study of plasminogen activators in cancers and normal mucosae of human urinary bladder. Cancer Res 49:1067–1070

    PubMed  CAS  Google Scholar 

  103. Kirchheimer JC, Pflüger H, Hienert G, Binder BR (1985) Increased urokinase activity to antigen ratio in human renal-cell carcinoma. Int J Cancer 35:737–741

    Article  PubMed  CAS  Google Scholar 

  104. Hienert G, Kirchheimer JC, Pflüger H, Binder BR (1988) Urokinase-type plasminogen activator as a marker for the formation of distant metastases in prostatic carcinomas. J Urol 140:1466–1469

    PubMed  CAS  Google Scholar 

  105. Kirchheimer JC, Koller A, Binder BR (1984) Isolation and characterization of plasminogen activators from hyperplastic and malignant prostate tissue. Biochim Biophys Acta 797:256–265

    Article  PubMed  CAS  Google Scholar 

  106. Kirchheimer JC, Pflüger H, Ritsehl P, Hienert G, Binder BR (1985) Plasminogen activator activity in bone metastases of prostatic carcinomas as compared to primary tumors. Invasion Metastasis 5:344–355

    PubMed  CAS  Google Scholar 

  107. Wojtukiewicz MZ, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Moritz TE, Rousseau SM, Stump DC (1991) Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue. Cancer 67:1377–1383

    Article  PubMed  CAS  Google Scholar 

  108. Markus G, Takita H, Camiolo SM, Corasanti JG, Evers JL, Hobika GH (1980) Content and characterization of plasminogen activators in human lung cancer and normal lung tissue. Cancer Res 40:841–848

    PubMed  CAS  Google Scholar 

  109. De Bruin PAF, Griffioen G, Verspaget HW, Verheijen JH, Dooijewaard G, van den Ingh HF, Lamers CBHW (1988) Plasminogen activator profiles in neoplastic tissues of the human colon. Cancer Res 48:4520–4524

    PubMed  Google Scholar 

  110. Veale D, Needham G, Harris AL (1990) Urokinase receptors in lung cancer and normal lung. Anticancer Res 10:417–421

    PubMed  CAS  Google Scholar 

  111. Hata M (1989) The study of plasminogen activator in renal carcinoma with special remarks on urokinase type plasminogen activator. Nippon Hinyokika Gakkai Zasshi 80:1558–1565

    PubMed  CAS  Google Scholar 

  112. Kirchheimer JC, Huber K, Polterauer P, Binder BR (1985) Urokinase antigen in plasma of patients with liver cirrhosis and hepatoma. Thromb Haemost 54:617–618

    PubMed  CAS  Google Scholar 

  113. Whitney CW, Satyaswaroop PG, Mörtel R (1985) Plasminogen activator activity in human endometrial carcinoma. Gynecol Oncol 22:97–104

    Article  PubMed  CAS  Google Scholar 

  114. Soszka T, Olszewski K (1986) Plasminogen activators and their inhibitors in normal, hyperplastic and carcinomatous human endometrium. Thromb Res 42:835–846

    Article  PubMed  CAS  Google Scholar 

  115. Oka T, Ishida T, Nishino T, Sugimachi K (1991) Immunohistochemical evidence of urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma. Cancer Res 51:3522–3525

    PubMed  CAS  Google Scholar 

  116. Camiolo SM, Markus G, Piver MS (1987) Plasminogen activator content of gynecological tumors and their metastases. Gynecol Oncol 26:364–373

    Article  PubMed  CAS  Google Scholar 

  117. Takahasi K, Gojobori T, Tanifuji M (1991) Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line. Exp Cell Res 192:405–413

    Article  Google Scholar 

  118. Plow EF, Freaney DE, Plescia J, Miles LA (1986) The plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type. J Cell Biol 103:2411–2420

    Article  PubMed  CAS  Google Scholar 

  119. Estreicher A, Wohlwend A, Belin D, Schleuning W-D, Vassalli J-D (1989) Characterization of the cellular binding site for the urokinase-type plasminogen activator. J Biol Chem 264:1180–1189

    PubMed  CAS  Google Scholar 

  120. Corasanti JG, Celik C, Camiolo SM, Mittelman A, Evers JL, Barbasch A, Hobika GH, Markus G (1980) Plasminogen activator content of human colon tumors and normal mucosae: separation of enzymes and partial purification. J Natl Cancer Inst 65:345–35

    PubMed  CAS  Google Scholar 

  121. Markus G, Camiolo SM, Kohga S, Madeja JM, Mittelman A (1983) Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors. Cancer Res 43:5517–5522

    PubMed  CAS  Google Scholar 

  122. Camiolo SM, Greco WR (1986) Plasminogen activator content of human tumor and adjacent normal tissue measured with fibrin and non-fibrin assays. Cancer Res 46:1788–1794

    PubMed  CAS  Google Scholar 

  123. Gelister JSK, Mamoud M, Lewin MR, Gaffney PJ, Boulos PB (1986) Plasminogen activators in human colorectal neoplasia. Br Med J 293:728–731

    Article  CAS  Google Scholar 

  124. DeBruin PAF, Verspaget HW, Griffioen G, Verheijen JH, Lamers CBHW (1986)Plasminogen activator activity in colonic polyp carcinoma sequence. Gut 27:A1267

    Google Scholar 

  125. Colombi M, Barlati S, Magdalenai H, Fiszer-Szafarz B (1984) Relationship between multiple forms of plasminogen activator in human breast tumors and plasma and the presence of metastases in lymph nodes. Cancer Res 44: 2971–2975

    PubMed  CAS  Google Scholar 

  126. Hayashi S, Yamada K (1990) Properties of urokinase type-plasminogen activator found in chest fluid. Nippon Ketsueki Gakkai Zasshi 53:105–115

    PubMed  CAS  Google Scholar 

  127. Mitsubayashi S, Akiyama T, Kurita T, Okada K, Bando H, Sakai T, Matsuo O (1987)Plasminogen activators in bladder tumors. Urol Res 15:335–339

    Article  PubMed  CAS  Google Scholar 

  128. Constantini V, Zacharski LR, Memoli VA, Kudryk BJ, Rousseau SM, Stump DC (1991) Occurrence of components of fibrinolysis pathways in situ in neoplastic human breast tissue. Cancer Res 51:354–358

    Google Scholar 

  129. Hienert G, Kirchheimer JC, Christ G, Pflüger H, Binder BR (1988) Plasma urokinase-type plasminogen activator correlates to bone scintigraphy in prostatic carcinoma. Eur Urol 15:256–258

    PubMed  CAS  Google Scholar 

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  1. Frauenklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, W-8000, München 80, Germany

    M. Schmitt, F. Jänicke, N. Chucholowski, L. Goretzki, N. Moniwa, E. Schüren, O. Wilhelm & H. Graeff

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  1. M. Schmitt
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  2. F. Jänicke
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  3. N. Chucholowski
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  4. L. Goretzki
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  5. N. Moniwa
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  6. E. Schüren
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  7. O. Wilhelm
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  1. Abteilung für Klinische Chemie, Medizinische Klinik, Universitäts-Krankenhaus Eppendorf, Martinistraße 52, W-2000, Hamburg 20, Germany

    Christoph Wagener

  2. Diagnostische Forschung E. Merck, Frankfurter Straße 250, W-6100, Darmstadt, Germany

    Siegfried Neumann

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© 1993 Springer-Verlag Berlin Heidelberg

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Schmitt, M. et al. (1993). Biological and Clinical Relevance of the Tumor-Associated Serine Protease uPA. In: Wagener, C., Neumann, S. (eds) Molecular Diagnostics of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77521-5_12

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  • DOI: https://doi.org/10.1007/978-3-642-77521-5_12

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