143
Views
25
CrossRef citations to date
0
Altmetric
Research Article

Tumor-Associated Proteolytic Factors uPA and PAI-1: Critical Appraisal of Their Clinical Relevance in Breast Cancer and Their Integration into Decision-Support Algorithms

, , , &
Pages 179-201 | Published online: 10 Oct 2008

REFERENCES

  • Reuning U, Magdolen V, Wilhelm O, Fischer K, Lutz V, Graeff H, Schmitt M. Multifunctional potential of the plasminogen activation system in tumor invasion and metastasis (review). Int J Oncol 1998; 13: 893–906
  • Andreasen P A, Egelund R, Petersen H H. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 2000; 57: 25–40
  • Preissner K T, Kanse S M, May A E. Urokinase receptor: a molecular organizer in cellular communication. Curr Opin Cell Biol 2000; 12: 621–628
  • Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3: 932–943
  • Rosenberg S. The urokinase-type plasminogen activator system in cancer and other pathological conditions: introduction and perspective. Curr Pharm Des 2003; 9: 4p, (abst.)
  • Reuning U, Sperl S, Kopitz C, Kessler H, Kruger A, Schmitt M, Magdolen V. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR): development of antagonists of uPA/uPAR interaction and their effects in vitro and in vivo. Curr Pharm Des 2003; 9: 1529–1543
  • Rosenberg S. New developments in the urokinase-type plasminogen activator system. Expert Opin Ther Targets 2001; 5: 711–722
  • Stefansson S, McMahon G A, Petitclerc E, Lawrence D A. Plasminogen activator inhibitor-1 in tumor growth, angiogenesis and vascular remodeling. Curr Pharm Des 2003; 9: 1545–1564
  • Andreasen P A, Kjoller L, Christensen L, Duffy M J. The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 1997; 72: 1–22
  • Schmitt M, Harbeck N, Thomssen C, Wilhelm O, Magdolen V, Reuning U, Ulm K, Höfler H, Jänicke F, Graeff H. Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 1997; 78: 285–296
  • Schmitt M, Wilhelm O G, Reuning U, Krüger A, Harbeck N, Lengyel E, Graeff H, Gänsbacher B, Kessler H, Bürgle M, Stürzebecher J, Sperl S, Magdolen V. The plasminogen activation system as a novel target for therapeutic strategies. Fibrinolysis 2000; 14: 114–132
  • Jänicke F, Prechtl A, Thomssen C, Harbeck N, Meisner C, Untch M, Sweep C G, Selbmann H K, Graeff H, Schmitt M, for the German Chemo N0Study Group. Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 2001; 93: 913–920
  • Look M P, van Putten W L, Duffy M J, Harbeck N, Brünner N, Kates R, Fernö M, Eppenberger S, Spyratos F, Thomssen C, Sweep C GJ, Peyrat J P, Martin P M, Blankenstein M A, Magdelenat H, Quillien-Pouvreau V, Daver, Ricolleau G, Daxenbichler G, Cufer T, Bendahl P O, Lisboa B, Ulm K, Christensen I J, Meijer-van Gelder M E, Fiets E, Manders P, Broët P, Romain S, Windbichler G, Borstnar S, Beex L VRM, Jänicke F, Klijn J GM, Eppenberger U, Schmitt M, Foekens J A. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J Natl Cancer Inst 2002; 94: 116–128
  • Harbeck N, Kates R E, Look M P, Meijer-van Gelder M E, Klijn J GM, Jänicke F, Krüger A, Kiechle M, Schmitt M, Foekens J A. Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (n = 3424). Cancer Res 2002; 62: 4617–4622
  • Harbeck N, Kates R E, Schmitt M, Gauger K, Kiechle M, Jänicke F, Thomssen C, Look M P, Foekens J A. Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer. Clin Breast Cancer 2004; 5: 348–352
  • Schmitt M, Harbeck N, Daidone M G, Brünner N, Duffy M J, Foekens J A, Sweep F CGJ. Identification, validation, and clinical implementation of tumor-associated biomarkers to improve therapy concepts, survival, and quality of life of cancer patients: Tasks of the Receptor and Biomarker Group of the European Organization for Research and Treatment of Cancer. Int J Oncol 2004; 25: 1397–1406
  • Harbeck N, Kates R E, Gauger K, Willems A, Kiechle M, Magdolen V, Schmitt M. Urokinase-type plasminogen activator uPA and its inhibitor PAI-1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer. Thrombosis Haemostasis 2004; 91: 450–456
  • Duffy M J, O'Grady P, Devaney D, O'Siorain L, Fennelly J J, Lijnen H J. Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report. Cancer 1988; 62: 531–533
  • Jänicke F, Schmitt M, Ulm K, Gossner W, Graeff H. Urokinase-type plasminogen activator antigen and early relapse in breast cancer. Lancet 1989; 2: 1049
  • 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; 4: 69–78
  • Jänicke F, Schmitt M, Graeff H. Clinical relevance of the urokinase-type and tissue-type plasminogen activators and of their type 1 inhibitor in breast cancer. Semin Thromb Hemost 1991; 17: 303–312
  • Jänicke F, Schmitt M, Pache L, Ulm K, Harbeck N, Höfler H, Graeff H. Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res Treat 1993; 24: 195–208
  • Foekens J A, Schmitt M, van Putten W L, Peters H A, Kramer M D, Jänicke F, Klijn J GM. Plasminogen activator inhibitor-1 and prognosis in primary breast cancer. J Clin Oncol 1994; 12: 1648–1658
  • Grondahl-Hansen J, Peters H A, van Putten W L, Look M P, Pappot H, Ronne E, Dano K, Klijn J G, Brunner N, Foekens J A. Prognostic significance of the receptor for urokinase plasminogen activator in breast cancer. Clin Cancer Res 1995; 1: 1079–1087
  • Ferno M, Bendahl P O, Borg A, Brundell J, Hirschberg L, Olsson H, Killander D. Urokinase plasminogen activator, a strong independent prognostic factor in breast cancer, analysed in steroid receptor cytosols with a luminometric immunoassay. Eur J Cancer 1996; 32A: 793–801
  • Eppenberger U, Kueng W, Schlaeppi J M, Roesel J L, Benz C, Mueller H, Matter A, Zuber M, Luescher K, Litschgi M, Schmitt M, Foekens J A, Eppenberger-Castori S. Markers of tumor angiogenesis and proteolysis independently define high-and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 1998; 16: 3129–3136
  • Kim S J, Shiba E, Kobayashi T, Yayoi E, Furukawa J, Takatsuka Y, Shin E, Koyama H, Inaji H, Takai S. Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type-1, and tissue-type PA antigen levels in node-negative breast cancer: a prospective study on multicenter basis. Clin Cancer Res 1998; 4: 177–182
  • Kute T E, Grondahl-Hansen J, Shao S M, Long R, Russell G, Brünner N. Low cathepsin D and low plasminogen activator type 1 inhibitor in tumor cytosols defines a group of node negative breast cancer patients with low risk of recurrence. Breast Cancer Res Treat 1998; 47: 9–16
  • Knoop A, Andreasen P A, Andersen J A, Hansen S, Laenkholm A V, Simonsen A C, Andersen J, Overgaard J, Rose C. Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer. Br J Cancer 1998; 77: 932–940
  • Bouchet C, Hacene K, Martin P M, Becette V, Tubiana-Hulin M, Lasry S, Oglobine J, Spyratos F. Dissemination risk index based on plasminogen activator system components in primary breast cancer. J Clin Oncol 1999; 17: 3048–3057
  • Foekens J A, Peters H A, Look M P, Portengen H, Schmitt M, Kramer M D, Brunner N, Janicke F, Meijer-van Gelder M E, Henzen-Logmans S C, van Putten W L, Klijn J G. The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res 2000; 60: 636–643
  • Konecny G, Untch M, Arboleda J, Wilson C, Kahlert S, Boettcher B, Felber M, Beryt M, Lude S, Hepp H, Slamon D, Pegram M. Her-2/neu and urokinase-type plasminogen activator and its inhibitor in breast cancer. Clin Cancer Res 2001; 2448–2457
  • Cufer T, Borstnar S, Vrhovec I. Prognostic and predictive value of the urokinase-type plasminogen activator (uPA) and its inhibitors PAI-1 and PAI-2 in operable breast cancer. Int J Biol Markers 2003; 18: 106–115
  • Hansen S, Overgaard J, Rose C, Knoop A, Laenkholm A V, Andersen J, Sorensen F B, Andreasen P A. Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients. Br J Cancer 2003; 88: 102–108
  • Zemzoum I, Kates R E, Ross J S, Dettmar P, Dutta M, Henrichs C, Yurdseven S, Höfler H, Kiechle M, Schmitt M, Harbeck N. Invasion factors uPA/PAI-1 and HER2 status provide independent and complementary information on patient outcome in node-negative breast cancer. J Clin Oncol 2003; 21: 1022–1028
  • Bouchet C, Ferrero-Pous M, Hacene K, Becette V, Spyratos F. Limited prognostic value of c-erbB-2 compared to uPA and PAI-1 in primary breast carcinoma. Int J Biol Markers. 2003; 18: 207–217
  • Manders P, Tjan-Heijnen V C, Span P N, Grebenchtchikov N, Geurts-Moespot A, van Tienoven D T, Beex L V, Sweep F C. Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma. Cancer 2004; 101: 486–494
  • Meo S, Dittadi R, Peloso L, Gion M. The prognostic value of vascular endothelial growth factor, urokinase plasminogen activator and plasminogen activator inhibitor-1 in node-negative breast cancer. Int J Biol Markers 2004; 19: 282–288
  • Harbeck N, Kates R E, Schmitt M. Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J Clin Oncol 2002; 20: 1000–1007
  • Hayes D F, Bast R, Desch C E, Fritsche H, Jr, Kemeny N E, Jessup J M, Locker G Y, Macdonald J S, Mennel R G, Norton L, Ravdin P, Taube S, Winn R J. A tumor marker utility grading system (TMUGS): a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 1996; 88: 1456–1466
  • Harbeck N, Thomssen C, Berger U, Ulm K, Kates R, Höfler H, Jänicke F, Graeff H, Schmitt M. Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following first relapse. Breast Cancer Res Treat 1999; 54: 147–157
  • Harbeck N, Meisner C, Prechtl A, Untch M, Selbmann H K, Sweep C GJ, Graeff H, Schmitt M, Jänicke F, Thomssen C, for the German Chemo-N0Study Group. Level-I evidence for prognostic and predictive impact of uPA and PAI-1 in node-negative breast cancer provided by second scheduled analysis of multicenter Chemo-N0 therapy trial. Breast Cancer Res Treat 2001; 69: 213
  • Look M, van Putten W, Duffy M, Harbeck N, Christensen I J, Thomssen C, Kates R, Spyratos F, Fernö M, Eppenberger-Castori S, Sweep C GJ, Ulm K, Peyrat J P, Martin P M, Magdelenat H, Brünner N, Duggan C, Lisboa B, Bendahl P O, Quillien V, Daver A, Ricolleau G, Meijer-van Gelder M E, Manders P, Fiets E, Blankenstein M A, Broët P, Romain S, Daxenbichler G, Windbichler G, Cufer T, Borstnar S, Kueng W, Beex L VRM, Klijn J GM, Eppenberger U, Jänicke F, Schmitt M, Foekens J A. Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients. Thromb Haemost 2003; 90: 538–548
  • Sweep C G, Geurts-Moespot J, Grebenschikov N, de Witte J H, Heuvel J J, Schmitt M, Duffy M J, Janicke F, Kramer M D, Foekens J A, Brunner N, Brugal G, Pedersen A N, Benraad T J. External quality assessment of trans-European multicentre antigen determinations (enzyme-linked immunosorbent assay) of urokinase-type plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in human breast cancer tissue extracts. Br J Cancer 1998; 78: 1434–1441
  • Sweep F C, Fritsche H A, Gion M, Klee G G, Schmitt M. Considerations on development, validation, application, and quality control of immuno(metric) biomarker assays in clinical cancer research: an EORTC-NCI working group report. Int J Oncol 2003; 23: 1715–1726
  • 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
  • Schmitt M, Lienert S, Prechtel D, Sedlaczek E, Welk A, Reuning U, Magdolen V, Jänicke F, Sweep C GJ, Harbeck N. The urokinase protease system as a target for breast cancer prognosis and therapy: technical considerations. Journal of Clinical Ligand Assay 2002; 25: 43–52
  • Schmitt M, Sturmheit A S, 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 2006; 120: 245–265
  • Harbeck N, Alt U, Krüger A, Berger U, Thomssen C, Jänicke F, Kates R, Schmitt M. Prognostic impact of proteolytic factors (uPA, PAI-1, cathepsins B, D, L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 2001; 7: 2757–2764
  • Harbeck N, Schmitt M, Kates R E, Kiechle M, Zemzoum I, Jänicke F, Thomssen C. Clinical utility of uPA/PAI-1 determination in primary breast cancer tissue for individualized therapy concepts. Clin Breast Cancer 2002; 3: 196–200
  • Manders P, Tjan-Heijnen V C, Span P N, Grebenchtchikov N, Foekens J A, Beex L VAM, Sweep C GJ. Predictive impact of urokinase-type plasminogen activator: plasminogen activator inhibitor type-1 complex on the efficacy of adjuvant systemic therapy in primary breast cancer. Cancer Res 2004; 64: 659–664
  • Foekens J A, Look M P, Peters H A, van Putten W L, Portengen H, Klijn J G. 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; 17(87)751–756
  • Meijer-van Gelder M E, Look M P, Peters H A, Schmitt M, Brunner N, Harbeck N, Klijn J G, Foekens J A. Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Res 2004; 64: 4563–4568
  • Manders P, Tjan-Heijnen V C, Span P N, Grebenchtchikov N, Geurts-Moespot A J, van Tienoven D T, Beex L VAM, Sweep C GJ. The complex between urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-I) independently predicts response to first-line endocrine therapy in advanced breast cancer. Thromb Haemost 2004; 9: 514–521
  • Goldhirsch A, Glick J H, Gelber R D, Coates A S, Thurlimann B, Senn H J. Panel Members. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 2005; 16: 1569–1583
  • Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–1717
  • Ravdin P M, Siminoff L A, Davis G J, Mercer M B, Hewlett J, Gerson N, Parker H L. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001; 19: 980–991
  • Olivotto I A, Bajdik C D, Ravdin P M, Speers C H, Coldman A J, Norris B D, Davis G J, Chia S K, Gelmon K A. Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 2005; 23: 2716–2725
  • Kates R, Harbeck N, Ulm K, Graeff H, Schmitt M. Progress in decision support and forecasting in breast cancer using likelihood-based neural network analysis. Breast Cancer Res Treat 1999; 57: 42, (abst.)
  • Ravdin P M, Siminoff I A, Harvey J A. Survey of breast cancer patients concerning their knowledge and expectations of adjuvant therapy. J Clin Oncol 1998; 16: 515–521
  • van't Veer L J, Paik S, Hayes D F. Gene expression profiling of breast cancer: a new tumor marker. J Clin Oncol 2005; 23: 1631–1635
  • Muehlenweg B, Sperl S, Magdolen V, Schmitt M, Harbeck N. (alle Autoren) Interference with the urokinase plasminogen activator system: a promising therapy concept for solid tumors. Exp Opin Biol Ther 2001; 1: 683–691
  • Setyono-Han B, Sturzebecher J, Schmalix W A, Muehlenweg B, Sieuwerts A M, Timmermans M, Magdolen V, Schmitt M, Klijn J G, Foekens J A. Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1. Thromb Haemost 2005; 93: 779–786
  • Kates R, Schmitt M, Harbeck N. Advanced statistical methods for the definition of new staging models. Recent Results Cancer Res 2003; 162: 101–113
  • Elston C W, Ellis I O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403–410
  • Liestol K, Anderson P, Anderson U. Survival analysis and neural nets. Stat Med 1994; 13: 1189–1120
  • Faraggi D, Simon R. A neural network model for survival data. Stat Med 1995; 14: 73–82
  • Biganzoli E, Boracchi P, Mariani L, Marubini E. Feed forward neural networks for the analysis of censored survival data: A partial logistic regression approach. Stat. Med. 1998; 17: 1169
  • Hornberger J, Cosler L, Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node–negative, estrogen-receptor–positive, early-stage breast cancer. Am J Managed Care 2005; 11: 313–324
  • Schumacher M, Rossner R, Vach W. Neural Networks and logistic regression: Part I. Comp Stat Data Analysis 1996; 21: 661–682
  • Vach W, Rossner R, Schumacher M. Neural networks and logistic regression: Part II. Comp Stat Data Analysis 1996; 21: 683–701
  • Slamon D J, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–792

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.