Clinical Impact of the Plasminogen Activation System in Tumor Invasion and Metastasis: Prognostic Relevance and Target for Therapy

• References

• 1 Wattenberg LW. Prevention - Therapy - Basic Science and the resolution of the cancer problem: Presidential address. Cancer Res 1993; 53: 5890-5896
• 2 Schmitt M, Jänicke F, Graeff H. Tumor-associated proteases. Fibrinolysis 1992; 06 suppl 04 3-26
• 3 Schmitt M, Wilhelm O, Jänicke F, Magdolen V, Reuning U, Ohi H, Moniwa N, Kobayashi H, Weidle U, Graeff H. Urokinase-type plasminogen activator (uPA) and its receptor (CD87). A new target in tumor invasion and metastasis. J Obstet Gynaecol 1995; 21: 151-16
• 4 Duffy MJ. Proteases as prognostic markers. Clin Cancer Res 1996; 02: 613-618
• 5 Duffy MJ. The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis 1992; 10: 145-155
• 6 Brünner N, Pyke C, Hansen CH, Romer J, Grondahl-Hansen J, Dano K. Urokinase plasminogen activator (uPA) and its type 1 inhibitor (PAI-1): regulators of proteolysis during cancer invasion and prognostic parameters in breast cancer. Cancer Treat Res 1994; 71: 299-309
• 7 Ploug M, Behrendt N, Lober D, Dano K. Protein structure and membrane anchorage of the cellular receptor for urokinase-type plasminogen activator. Seminars in Thrombosis and Hemostasis 1991; 17: 183-193
• 8 Estreicher A, Muhlhauser J, Carpentier JL, Orci L, Vassalli JD. 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 1990; 111: 783-792
• 9 Conesi M, Blasi F. Urokinase / urokinase receptor system: Internalization / degradation of urokinase-serpin complexes: Mechanism and regulation. Biol Chem Hoppe-Seyler 1995; 376: 143-155
• 10 Liu G, Shuman MA, Cohen RL. Co-expression of urokinase, urokinase receptor and PAI-1 is necessary for optimum invasiveness of cultured lung cancer cells. Int J Cancer 1995; 60: 501-506
• 11 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 1996; 155: 858-862
• 12 Ganesh S, Sier CF, Griffioen G, Vloedgraven HJ, de Boer A, Welvaart K, van de Velde CJ, van Krieken JH, Verheijen JH, Lamers CB, Verspaget HW. Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer. Cancer Res 1994; 54: 4065-4071
• 13 Hasui Y, Marutsuka K, Asada Y, Osada Y. Prognostic value of urokinase-type plasminogen activator in patients with superficial bladder cancer. Urology 1996; 47: 34-37
• 14 Jänicke F, Schmitt M, Pache L, Ulm K, Harbeck N, Höfler H, Graeff H. Urokinase (uPA) and its inhibitor PAI-1 are strong, independent prognostic factors in node-negative breast cancer. Breast Cancer Res Treatm 1993; 24: 195-208
• 15 Kuhn W, Pache L, Schmalfeldt B, Dettmar P, Schmitt M, Jänicke F, Graeff H. Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy. Gynecol Oncol 1994; 55: 401-409
• 16 Nekarda H, Schmitt M, Ulm K, Wenninger A, Vogelsang H, Becker K, Roder JD, Fink U, Siewert JR. Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer. Cancer Res 1994; 54: 2900-2907
• 17 Pedersen H, Brunner N, Francis D, Osterlind K, Ronne E, Hansen HH, Dano K, Grondahl-Hansen J. 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
• 18 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 1994; 54: 6539-6548
• 19 Nekarda H, Roder J, Vogelsang H, Becker K, Siewert JR. Prognosti impact of invasion-associated proteolyti factors in ductal carcinoma of the pancreas. BIOMED-1 Meeting. 1996. Leiden: Abstract 32
• 20 Choong PFM, Ferno M, Akerman M, Willen H, Langstrom E, Gustafson P, Alvegard T, Rydholm A. Urokinase-plasminogen- activator levels and prognosis in 69 soft-tissue sarcomas. Intern J Cancer 1996; 69: 268-272
• 21 Bindal AK, Hammoud M, Shi WM, Wu SZ, Sawaya R, Rao JS. Prognostic significance of proteolytic enzymes in human brain tumors. J. Neurooncol 1994; 22: 101-110
• 22 Gleeson NC, Gonsalves R, Bonnar J. Plasminogen activator inhibitors in endometrial adenocarcinoma. Cancer 1993; 72: 1670-1672
• 23 Besser D, Urich M, Sakaue M, Messerschmitt A, Ballmer-Hofer K, Nagamine Y. Urokinase-type plasminogen activator gene regulation by polyoma virus middle-T antigen. Oncogene 1995; 11: 2383-2391
• 24 Shevelev Al, Kondratov RV, Rybalkin IN, Prasolov VS. Expression of human urokinase in inoculated rodent cells. Loss of introns during gene transfer using a retroviral vector. Mol. Biol. Mosk 1992; 26: 208-217
• 25 Horrevoets AJ, Smilde AE, Fredenburgh JC, Pannekoek H, Nesheim ME. The activation-resistant conformation of recombinant human plasminogen is stabilized by basic residues in the amino-terminal hinge region. J Biol Chem 1995; 270: 15770-15776
• 26 Achbarou A, Kaiser S, Tremblay G, Ste-Marie LG, Brodt P, Goltzman D, Rabbani SA. Urokinase overproduction results in increased skeletal metastasis by prostate cancer cells in vivo. Cancer Res 1994; 54: 2372-2377
• 27 Lieber A, Vrancken-Peeters MJ, Meuse L, Fausto N, Perkins J, Kay MA. Adenovirus-mediated urokinase gene transfer induces liver regeneration and allows for efficient retrovirus transduction of hepatocytes in vivo. Proc Natl Acad Sci USA 1995; 92: 6210-6214
• 28 Chucholowski N, Schmitt M, Rettenbeiger P, Schüren E, Moniwa N, Goretzki L, Wilhelm O, Weidle U, Jänicke F, Graeff H. Flow cytofluorometric analysis of the urokinase receptor (uPA-R) on tumor cells by fluorescent uPA-ligand or monoclonal antibody #3936. Fibrinolysis 1992; 06 suppl 04 95-102
• 29 Andreasen PA, Sottrup-Jensen L, Kloller L, Nykjaer A, Moestrup SK, Munch-Petersen C, Gliemann J. Receptor-mediated endocytosis of plasminogen activators and activator/ inhibitor complexes. FEBS Lett 1994; 338: 239-245
• 30 Ploug M, Behrendt N, Lober D, Dano K. Protein structure and membrane anchorage of the cellular receptor for urokinase- type plasminogen activator. Seminars in Thromb Hemostas 1991; 17: 183-193
• 31 Nykjaer A, Petersen CM, Moller B, Jensen PH, Moestrup SK, Holtet TL, Etzerod M, Thorgersen HC, Munch M, Andreasen PA, Gliemann J. Purified alpha-2 macroglobulin receptor / LDL receptor-related protein binds urokinase plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor- bound complexes. J Biol Chem 1992; 267: 14543-14546
• 32 Magdolen V, Rettenberger P, Koppitz M, Goretzki L, Kessler H, Weidle UH, Konig B, Graeff H, Schmitt M, Wilhelm O. Systematic mutational analysis of the receptor-binding region of the human urokinase-type plasminogen activator. Eur J Biochem 1996; 237: 743-751
• 33 Goodson RJ, Doyle MV, Kaufman SE, Rosenberg S. High affinity urokinase receptor antagonists identified with bacteriophage peptide display. Proc Natl Acad Sci USA 1994; 91: 7129-7133
• 34 Nielsen LS, Kellermann GM, Behrendt N, Picone R, Dano K, Blasi F. A55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification. J Biol Chem 1988; 263: 2358-2363
• 35 Ploug M, Ronne E, Behrendt N, Jensen AL, Blasi F, Dano K. Cellular receptor for urokinase plasminogen activator: Carboxyl- terminal processing and membrane anchoring by glycosyl- phosphatidylinositol. J Biol Chem 1991; 266: 1926-1933
• 36 Dumler I, Petri T, Schleuning WD. Tyrosine phosphorylation of a 38 kDa protein upon interaction of urokinase-type plasminogen activator (u-PA) with its cellular receptor. Excerpta Medica International Congress Series 1993; 1041: 163-169
• 37 Miles LA, Plow EF. Plasminogen receptors: Ubiquitous sites for cellular regulation of fibrinolysis. Fibrinolysis 1988; 02: 61-71
• 38 Xing RH, and Rabbani SA. Overexpression of urokinase receptor in breast cancer cells results in increased tumor invasion growth and metastasis. Int J Cancer 1996; 67: 423-429
• 39 Kanse S, Kost C, Wilhelm O, Andreasen PA, Preissner KT. The urokinase receptor is a major vitronectin-binding protein on endothelial cells. Exp Cell Res 1996; 224: 344-353
• 40 Wei Y, Lukashev M, Simon DI, Bodary SC, Rosenberg S, Doyle MV, Chapman HA. Regulation of integrin function by the urokinase receptor. Science 1996; 273: 1551-1555
• 41 Felsenfeld DP, Choquet D, Sheetz MP. Ligand binding regulates the directed movement of bl integrins on fibroblasts. Nature 1996; 383: 438-440
• 42 Benraad TJ, Geurts-Moespot J, Grondahl-Hansen J, Schmitt M, Heuvel JJTM, de Witte JH, Foekens JA, Leake RE, Brunner N, Sweep CGJ. Immunoassays (ELISA) of urokinase-type plasminogen activator (uPA): Report of an EORTC/BIOMED-1 workshop. Eur J Cancer 1996; 32 A 1371-1381
• 43 Gohring UJ, Scharl A, Thelen U, Ahr A, Crombach G. Comparative prognostic value of cathepsin D and urokinase plasminogen activator detected by immunohistochemistry, in primary breast carcinoma. Anticancer Research 1996; 16: 1011-1018
• 44 Costantini V, Sidoni A, Deveglia R, Cazzato OA, Bellezza G, Ferri I, Bucciarelli E, Nenci GG. Combined overexpression of urokinase urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: An immunohistochemical comparison of normal, benign, and malignant breast tissues. Cancer 1996; 77: 1079-1088
• 45 Ito H, Yonemura Y, Fujita H, Tsuchihara K, Kawamura T, Nojima N, Fujimura T, Nose H, Endo Y, Sasaki T. Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer. Virchows Archiv - an Intern J Pathol 1996; 427: 487-496
• 46 Mulcahy HE, Duffy MJ, Gibbons D, McCarthy P, Parfrey NA, O’Donoghue DP, Sheahan K. Urokinase-type plasminogen activator and outcome in Dukes’ B colorectal cancer. Lancet 1994; 344: 583-584
• 47 McGuire WL, Clark GM. Prognostic factors and treatment decisions in axillary-node-negative breast cancer. New Engl J Med 326: 1756-1761
• 48 McGuire WL, Tandon AK, Allred DC, Chamness GC, Clark GM. How to use prognostic factors in axillary node-negative breast cancer patients. JNCI 1990; 82: 1006-1015
• 49 Duffy M, O’Grady P, Devaney D, O’Siorain L, Fennelly JJ, Lijnen HJ. Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Cancer 1988; 62: 531-533
• 50 Jänicke F, Schmitt M, Ulm K, Gössner W, Graeff H. Urokinase-type plasminogen activator antigen and early relapse in breast cancer. Lancet 1989; 8670: 1049
• 51 Jänicke F, Schmitt M, Hafter R, Hollrieder A, Babic R, Ulm K, Gössner W, Graeff H. Urokinase-type plasminogen activator (u-PA) antigen is a predictor of early relapse in breast cancer. Fibrinolysis 1990; 04: 69-78
• 52 Duffy MJ, Reilley D, O’Sullivan C, O’Higgins N, Fennelly JN, Andreasen P. Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer. Cancer Res 1990; 50: 6827-6829
• 53 Foekens JA, Schmitt M, van Putten WLJ, Peters HA, Bontenbal M, Jänicke F, Klijn JGM. Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients. Cancer Res 1992; 52: 6101-6105
• 54 Grondahl-Hansen J, Christensen IJ, Rosenquist C, Brünner N, Mouridsen HT, Dano K, Blichert-Toft M. High levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Research 1993; 53: 2513-2521
• 55 Jänicke F, Schmitt M, Graeff H. Clinical relevance of the urokinase-type and the tissue-type plasminogen activators and of their inhibitor PAI-1 in breast cancer. Seminars in Thromb Hemostas 1991; 17: 303-312
• 56 Foekens JA, Schmitt M, van PuttenWLJ, Peters HA, Jänicke F, Klijn JGM. Plasminogen activator inhibitor-1 and breast cancer metastasis. J Clin Oncol 1994; 12: 1648-1658
• 57 Duggan C, Maguire T, McDermott E, O’Higgins N, Fennelly JJ, Duffy MJ. Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer. Int J Cancer 1995; 61: 597-600
• 58 Grondahl-Hansen J, Peters HA, van Putten WLJ, Look MP, Pappot H, Ronne E, Dano K, Klijn JGM, Brünner N, Foekens JA. Prognostic significance of the receptor for urokinase plasminogen activator in breast cancer. Clinical Cancer Research 1995; 01: 1079-1087
• 59 Foucre D, Bouchet C, Hacene K, Pourreau-Schneider N, Gentile A, Martin PM, Desplaces A, Oglobine J. Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours. Br J Cancer 1991; 64: 926-932
• 60 Foekens JA, Buessecker F, Peters HA, Krainick U, van Putten WL, Look MP, Klijn JG, Kramer MD. Plasminogen activator inhibitor-2: prognostic relevance in 1012 patients with primary breast cancer. Cancer Res 1995; 55: 1423-1427
• 61 Sier CM, Vloedgraven HJM, Ganesh S, Griffioen G, Quax PH, Verheijen JH, Dooijewaard G, Welvaart K, van de Velde CJ, Lamers CB, Verspaget HW. Inactive urokinase and increased levels of its inhibitor type 1 in colorectal cancer liver metastasis. Gastroenterology 1994; 107: 1449-1456
• 62 Iozzo RV. Tumor stroma as a regulator of neoplastic behavior. Lab In vest 73: 157-160
• 63 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
• 64 Barbareschi M, Gasparini G, Morelli L, Forti S, Dalla PalmaP. Novel methods for the determination of the angiogenic activity of human tumors. Breast Cancer Res Treatm 1995; 36: 181-192
• 65 Ragno P, Montuori N, Rossi G. Urokinase-type plasminogen activator / type-2 plasminogen activator inhibitor complexes are not internalized upon binding to the urokinase-type plasminogen activator receptor in THP-1 cells. Interaction of urokinase-type plasminogen activator / type-2 plasminogen activator inhibitor complexes with the cell surface. Eur J Biochem 1995; 233: 514-519
• 66 Dickinson JL, Bates EJ, Ferrante A, Antalis TM. Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha- induced apoptosis. Evidence for an alternate biological function. J Biol Chem 1995; 270: 27894-27904
• 67 Wagner S, Atkinson MJ, Thanner S, Schmitt M, Wilhelm O, Rotter M, Höfler H. Type-1 plasminogen activator inhibitor in human renal cell carcinoma. J Pathol 1996; 179: 95-99
• 68 Van VeldhuizenPJ, Sadasivan R, Cherian R, Wyatt A. Urokinase-type plasminogen activator expression in human prostate carcinomas. Am J Med Sciences 1996; 312: 8-11
• 69 Yonemura Y, Nojima N, Kaji M, Fujimura T, Itoh H, Ninomiya MiyazakiI, Endo Y, Sasaki T. E-cadherin and urokinase-type plasminogen activator tissue status in gastric carcinoma. Cancer 1995; 76: 941-953
• 70 Naitoh H, Eguchi Y, Ueyama H, Kodama M, Hattori T. Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1,2 and plasminogen in colon cancer. Jpn J Cancer Res 1995; 86: 48-56
• 71 Itaya T, Motai H, Suzuki K, Baba S. Immunohistochemical study of fibrinolytic factors of head and neck squamous cell carcinomas. Nippon Jibiinkoka Gakkai Kaiho 98: 197-202
• 72 Parolini S, Flagiello D, Cinquetti A, Gozzi R, Cristini S, Cappiello J, Nicolai P, Rusnati M, Presta M, Tosatti MM. Up-regulatiOn of urokinase-type plasminogen activator in squamous cell carcinoma of human larynx. Br J Cancer 1996; 74: 1168-1174
• 73 Yamamoto M, Sawaya R, Mohanam S, Bindal AK, Bruner JM, Oka K, Rao VH, Tomonaga M, Nicolson GL, Rao JS. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo. Cancer Res 1994; 54: 3656-3661
• 74 Pyke C, Ralfkiaer E, Ronne E, Hoyer-Hansen G, Kirkeby L, Dano K. Immunohistochemical defection of the receptor for urokinase plasminogen activator in human colon cancer. Histopathology 1994; 24: 131-138
• 75 Sier CFM, Fellbaum C, Verspaget HW, Schmitt M, Griffioen G, Graeff H, Höfler H, Lamers CBHW. Immunolocalization of urokinase-type plasminogen activator (uPA) in adenomas and carcinomas of the human colon. Histopathology 1991; 19: 231-237
• 76 Gris JC, Schved JF, Mart-Double C, Mauboussin JM, Balmes P. Immunohistochemical study of tumor cell-associated plasminogen activators and plasminogen activator inhibitors in lung carcinomas. Chest 1993; 104: 08-13
• 77 Escot C, Zhao Y, Puech C, Rochefort H. Cellular localisation by in situ hybridisation of cathepsin D, stromelysin 3, and urokinase plasminogen activator RNAs in breast cancer. Breast Cancer Res Treatm 1996; 38: 217-226
• 78 Stoppelli MP, Tachetti C, Cubellis MV, Corti A, Hearing VJ, Cassani G, Appella E, Blasi F. Autocrine saturation of pro-urokinase receptors on human A431 cells. Cell 1986; 45: 675-684
• 79 Clark GM, Hilsenbeck SG. Integration of prognostic factors: can we predict breast cancer recurrences ?. In: Prospects in diagnosis and treatment of breast cancer. International Congress Series, Excerpta Medica 1050. Schmitt M, Graeff H, Kindermann G. eds Elsevier; Amsterdam: 1994. pp 177-186
• 80 Jänicke F, Thomssen C, Pache L, Schmitt M, Graeff H. Urokinase (uPA) and PAI-1 as selection criteria for adjuvant chemotherapy in axillary node-negative breast cancer patients. In: Prospects in diagnosis and treatment of cancer. International Congress Series, Excerpta Medica 1050. Schmitt M, Graeff H, Kindermann G. eds Elsevier; Amsterdam: 1994. pp 207-218
• 81 Dettmar P, Harbeck N, Thomssen C, Henselmann B, Prechtl A, Ulm K, Jänicke F, Höfler H, Graeff H, Schmitt M. Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in node-negative breast cancer. Br J Cancer. 1997 in press
• 82 Harbeck N, Dettmar P, Thomssen C, Pache L, Ziffer P, Fizi K, Jänicke F, Nathrath W, Schmitt M, Graeff H, Höfler H. Prognostic impact of tumor biological factors on survival in node-negative breast cancer. Anticancer Res. 1997 in press
• 83 Jänicke F, Pache L, Schmitt M, Ulm K, Thomssen C, Prechtl A, Graeff H. 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 1994; 54: 2527-2530
• 84 Schmitt M, Thomssen C, Ulm K, Seiderer A, Harbeck N, Höfler H, Jänicke F, Graeff H. Time-varying prognostic impact of tumor biological factors urokinase (uPA), PAI-1, and steroid hormone receptor status in primary breast cancer. Br J Cancer. 1997 in press
• 85 Cox DR. Regression models and life-tables. J R Stat Soc (B) 1972; 34: 187-200
• 86 Gray RJ. Flexible methods for analyzing survival data using splines, with applications to breast cancer prognosis. J Am Stat Association 1992; 87: 942-951
• 87 Foekens JA, Look MP, Peters HA, van PuttenWL, Portengen H, Klijn JG. Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. J Natl Cancer Inst 1995; 87: 751-756
• 88 Gleeson N, Gonsalves R, Bonnar J. The plasminogen activator urokinase and its inhibitor PAI-2 in endometrial cancer. Gynecol Oncol 1992; 47: 58-61
• 89 Gleeson N, Gonsalves R, Bonnar J. Uterine fibrinolytic enzymes in endometrial cancer. Eur J Gynaecol Oncol 1993; 14: 369-373
• 90 Hasui Y, Marutsuka K, Suzumiya J, Kitada S, Osada Y, Sumiyoshi A. The content of urokinase-type plasminogen antigen as a prognostic factor in urinary bladder cancer. Int J Cancer 1992; 50: 871-873
• 91 Hasui Y, Nishi S, Kitada S, Osada Y. Urokinase-type plasminogen activator antigen as a prognostic factor in bladder cancer. Nippon Hinyokika Gakkai Zasshi 1993; 84: 1624-1628
• 92 Hasui Y, Marutsuka K, Nishi S, Kitada S, Osada Y, Sumiyoshi A. The content of urokinase-type plasminogen activator and tumor recurrence in superficial bladder cancer. J Urol 1994; 151: 16-19
• 93 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. Cancer 1996; 78: 487-492
• 94 Lehmann K, Plas E, Gautschi K, Hauri D. Prognostic value of urokinase plasminogen activator for prostatic carcinoma. Urol Int 1994; 52: 159-161
• 95 Hewin DF, Savage PB, Alderson D, Vipond MN. Plasminogen activators in oesophageal carcinoma. Brit J Surgery 1996; 83: 1152-1155
• 96 Nekarda H, Siewert JR, Schmitt M, Ulm K. Tumour-associated proteolytic factors uPA and PAI-1 and survival in totally resected gastric cancer. Lancet 1994; 343: 117
• 97 Heiss MM, Babic R, Allgayer H, Gruetzner KU, Jauch KW, Loehrs U, Schildberg FW. Tumor associated proteolysis and prognosis: new functional risk factors in gastric cancer defined by the urokinase type plasminogen activator system. J Clin Oncol 1995; 13: 2084-2093
• 98 Heiss MM, Allgayer H, Gruetzner KU, Funke I, Babic R, Jauch KW, Schildberg FW. Individual development and uPA-receptor expression of disseminated tumor cells in bone marrow: A reference to early systemic disease in solid cancer. Nature Medicine 1995; 01: 1035-1039
• 99 Ganesh S, Sier CFM, Heerding MM, vanKrieken JHJM, Griffioen G, Welvaart K, vandeVelde CJH, Verheijen JH, Lamers CBHW, Verspaget HW. Prognostic value of the plasminogen activation system in patients with gastric carcinoma. Cancer 1996; 77: 1035-1043
• 100 Plebani M, Herszenyi L, Cardin R, Roveroni G, Carraro P, Paoli MD, Rugge M, Grigioni WF, Nitti D, Naccarato R. et-al Cysteine and serine proteases in gastric cancer. Cancer 1995; 76: 367-375
• 101 Maeda K, Chung YS, Sawada T, Ogawa Y, Onoda N, Nakata B, Kato Y, Sowa M. Combined evaluation of urokinase- type plasminogen activator and plasminogen activator inhibitor-2 expression in gastric carcinoma. Int J Oncology 1996; 08: 499-503
• 102 Verspaget HW, Sier CF, Ganesh S, Griffioen G, Lamers CB. Prognostic value of plasminogen activators and their inhibitors in colorectal cancer. Eur J Cancer 1995; 31 A 1105-1109
• 103 Ganesh S, Sier CF, Heerding MM, Griffioen G, Lamers CB, Verspaget HW. Urokinase receptor and colorectal cancer survival. Lancet 1994; 344 8919 401-402
• 104 Tatsuta S, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F. Combined expression of urokinase-type plasminogen activator and proliferating cell nuclear antigen at the deepest invasive portion correlates with colorectal cancer prognosis - clinical studies. Int J Oncol 1997; 10: 125-129
• 105 Sato T, Nishimura G, Yonemura Y, Nojima N, Ninomiya I, Fujimura T, Sugiyama K, Miwa K, Miyazaki I, Nonomura A. et al: Association of immunohistochemical detection of urokinase-type plasminogen activator with metastasis and prognosis in colorectal cancer. Oncology 1995; 52: 347-352
• 106 Buo L, Meling GI, Karlsrud TS, Johansen HAT, Aasen AO. Antigen levels of urokinase plasminogen activator and its receptor at the tumor-host interface of colorectal adenocarcinomas are related to tumor aggressiveness. Hum Pathol 1995; 26: 1133-1138
• 107 Hsu DW, Efird JT, Hedley-Whyte ET. Prognostic role of urokinase-type plasminogen activator in human gliomas. Am J Pathol 1995; 147: 114-123
• 108 Pedersen H, Grondahl-Hansen J, Francis D, Osterlind K, Hansen HH, Dano K, Brunner N. Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma. Cancer Res 1994; 54: 120-123
• 109 Zeillinger R, Eder S, Schneeberger C, Ullrich R, Speiser P, Swoboda H. Cathepsin D and PAI-1 expression in human head and neck cancer. Anticancer Research 1996; 16: 449-453
• 110 Hackel C, Czerniak B, Ayala AG, Radig K, Roessner A. Expression of plasminogen activators and plasminogen activator inhibitor 1 in dedifferentiated chondrosarcoma. Cancer 1997; 79: 53-58
• 111 Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 1985; 44: 139-266
• 112 Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature 1976; 261: 595-597
• 113 Engelhard NarangC, Homer R, Duncan H. Urokinase antisense oligodeoxynucleotides as a novel therapeutic agent for malignant glioma: In vitro and in vivo studies of uptake, effects and toxicity. Biochemical and Biophysical Research Communications 1996; 227: 400-405
• 114 Wilhelm O, Schmitt M, Höhl S, Senekowitsch R. Graeff Antisense inhibition of urokinase reduces spread of human ovarian cancer in mice. Clin Exp Metastasis 1995; 13: 296-302
• 115 Quattrone A, Fibbi G, Anichini E, Pucci M, Zamperini A, Capaccioli S, Del RossoM. Reversion of the invasive phenotype of transformed human fibroblasts by anti-messenger oligonucleotide inhibition of urokinase receptor gene expression. Cancer Res 1995; 55: 90-95
• 116 Reuning U, Wilhelm O, Nishiguchi T, Guerrini L, Blasi F, Graeff H, Schmitt M. Inhibition of NF-kB-REL A expression by antisense-oligodeoxynucleotides suppresses synthesis of urokinase-type plasminogen activator (uPA) but not its inhibitor PAI-1. Nucleic Acids Res 1995; 23: 3887-3893
• 117 Wilhelm O, Weidle U, Höhl S, Rettenberger P, Schmitt M, Graeff H. Recombinant soluble urokinase receptor as a scavenger for urokinase-type plasminogen activator (uPA). Inhibition of proliferation and invasion of human ovarian cancer cells. FEBS Lett 1994; 337: 131-134
• 118 Rettenberger P, Wilhelm O, Oi H, Weidle UH, Goretzki L, Koppitz M, Lottspeich F, König B, Pessara U, Kramer MD, Schmitt M, Magdolen V. A competitive chromogenic assay to study the functional interaction of urokinase-type plasminogen activator with its receptor. Biol Chem Hoppe-Seyler 1995; 376: 587-594
• 119 Goretzki L, Bognacki J, Koppitz M, Rettenberger P, Magdolen V, Creutzburg S, Hammelburger J, Weidle U, Wilhelm O, Kessler H, Graeff H, Schmitt M. Quantitative assessment of interaction of urokinase-type plasminogen activator (uPA) and its receptor (CD87) by use of a solid-phase uPA-ligand binding assay. Fibrinolysis. 1997. in press
• 120 Kobayashi H, Ohi H, Shinohara H, Sugimura M, Fujii T, Terao T, Schmitt M, Goretzki L, Chucholowski N, Jänicke F, Graeff H. Saturation of tumor cell surface receptors for urokinase-type plasminogen activator by amino-terminal fragment and subsequent effect on reconstituted basement membranes invasion. Br J Cancer 1993; 67: 537-544
• 121 Bürgle M, Kopitz M, Riemer C, Kessler H, König B, Weidle UH, Kellermann J, Lottspeich F, Graeff H, Schmitt M, Goretzki L, Reuning U, Wilhelm U, Magdolen V. Inhibition of the interaction of urokinase-type plasminogen activator (uPA) with its receptor (uPAR) by synthetic peptides. J. Biol Chem. 1997 in press
• 122 Kobayashi H, Ohi H, Sugimura M, Shinohara H, Fujii T, Terao T. Inhibition of in vitro ovarian cancer cell invasion by modulation of urokinase-type plasminogen activator and cathepsin. Cancer Res 1992; 52: 3610-3614
• 123 Min HY, Doyle LV, Vitt CR, Zandonella CL, Stratton-Thomas JR, Shuman MA, Rosenberg S. Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res 1996; 56: 2428-2433
• 124 Lu H, Yeh P, Guitton JD, Mabilat C, Desanlis F, Maury I, Legrand Y, Soria J, Soria C. Blockage of the urokinase receptor on cell surface: Construction and characterization of a hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin. FEBS Lett 1994; 356: 56-59
• 125 Rabbani SA, Harakidas P, Davidson DJ, Henkin J, Mazar AP. Prevention of prostate-cancer metastasis in vivo by a novel synthetic inhibitor of urokinase-type plasminogen activator (uPA). Intern J Cancerl 1995; 63: 840-845
• 126 Alonso DF, Farias EF, Ladeda V, Davel L, Puricelli L, Joffe EBD. Effects of synthetic urokinase inhibitors on local invasion and metastasis in a murine mammary tumor model. Breast Cancer Res Treatm 1996; 40: 209-223
• 127 Ono M, Izumi H, Yoshida S, Goto D, Jimi S, Kawahara N, Shono T, Ushiro S, Ryuto M, Kohno K, Sato Y, Kuwano M. Angiogenesis as a new target for cancer treatment. Cancer Chemotherapy and Pharmacology 1996; 38 Suppl. S78-S82
• 128 Carmeliet P, Collen D. Gene targeting and gene transfer studies of the biological role of the plasminogen/plasmin system. Thromb Haemostas 1995; 74: 429-436