New developments in the urokinase-type plasminogen activator system

Expert Opinion on Therapeutic Targets

Volumn 5, Issue 6, 2001, Pages 711-722

  Rosenberg, Steven ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Activation; Angiogenesis; Cancer; HIV; Integrin; Metastasis; PAI 1; Plasminogen; Urokinase; Urokinase receptor; Vitronectin

Indexed keywords

EID: 0037869895     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.5.6.711     Document Type: Review

References (116)

1. HOWE HL, WINGO PA, THUN MJ et al.: Annual report to the nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J. Nat. Cancer Inst. (2001) 93:824-842.
2. DRUKER BJ, TALPAZ M, RESTA DJ et al.: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukaemia. N. Engl. J. Med. (2001) 344:1031-1037.
3. COLOMER R, SHAMON LA, TSAI MS, LUPU R: Herceptin: from the bench to the clinic. Cancer Invest. (2001) 19:49-56.
4. REUNING U, MAGDOLEN V, WILHELM O et al.: Multifunctional potential of the plasminogen activation system in tumour invasion and metastasis. Int. J. Oncol. (1998) 13:893-906.
5. RABBANI SA: Metalloproteases and urokinase in angiogenesis and tumour progression. In Vivo (1998) 12:135-142.
6. NELSON AR, FINGLETON B, ROTHENBERG ML, MATRISIAN L: Matrix metalloproteinases: biologic activity and clinical implications. J. Clin. Oncol. (2000) 18:1135-1149.
7. ROSENBERG S: Modulators of the urokinase-type plasminogen activation system for cancer. Expert Opin. Ther. Patents (2000) 10:1843-1852.
8. CARMELIET P, COLLEN D: Development and disease in proteinase-deficient mice: role of the plasminogen, matrix metalloproteinase and coagulation system. Thromb. Res. (1998) 91:255-285.
9. ZHOU HM, NICHOLS A, MEDA P, VASSALLI JD: Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis. EMBO J. (2000) 19:4817-4826.
10. PLOW EG, HERREN T, REDLITZ A, MILES LA, HOOVER-PLOW J: The cell biology of the plasminogen system. FASEB J. (1995) 9:939-945.
11. ELLIS V, BERHRENDT N, DANO K: Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor. J. Biol. Chem. (1991) 266:12752-12758.
12. LIST K, JENSEN ON, BUGGE TH et al.: Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice. Biochemistry (2000) 39:508-515.
13. HANSEN AP, PETROS AM, MEADOWS RP et al.: Solution structure of the amino-terminal fragment of urokinase-type plasminogen activator. Biochemistry (1994) 33:4847-4864.
14. NIENABER VL, DAVIDSON D, EDALJI R et al.: Structure-directed discovery of potent non-peptidic inhibitors of human urokinase that access a novel binding subsite. Structure Fold. Des. (2000) 8:555-563.
15. ROLDAN AL, CUBELLIS MV, MASUCCI MT et al.: Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. (1990) 9:467-474.
16. ESTREICHER A, WOHLWEND A, BELIN D, SCHLEUNING WD, VASSALLI J: Characterisation of the cellular binding site for the urokinase-type plasminogen activator. J. Biol. Chem. (1989) 264:1180-1189.
17. PLOUG M, BEHRENDT N, LOBER D, DANO K: Protein structure and membrane anchorage of the cellular receptor for urokinase-type plasminogen activator. Sem. Thromb. Hemostasis (1991) 17:183-193.
18. FAZIOLI F, RESNATI M, SIDENIUS N et al.: A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. EMBO J. (1997) 16:7279-7286.
19. BLASI F: The urokinase receptor. A cell surface, regulated chemokine. APMIS (1999) 107:96-101.
20. APPELLA E, ULLRICH SJ, STOPPELLI MP et al.: The receptor-binding sequence of urokinase: a biological function for the growth-factor module of proteases. J. Biol. Chem. (1987) 262:4437-4440.
21. STRATTON-THOMAS JR, MIN HY, KAUFMAN SE et al.: Yeast expression and phagemid display of the human urokinase plasminogen activator epidermal growth factor-like domain. Prot. Engin. (1995) 8:463-470.
22. 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.
23. PLOUG M: Identification of specific sites involved in ligand binding by photoaffinity labelling of the receptor for the urokinase-type plasminogen activator. Residues located at equivalent positions in uPAR domains I and III participate in the assembly of a composite ligand-binding site. Biochemistry (1998) 37:16494-16505.
24. PLOUG M, OSTERGAARD S, HANSEN LB, HOLM A, DANO K: Photoaffinity labelling of the human receptor for urokinase-type plasminogen activator using a decapeptide antagonist. Evidence for a composite ligand-binding site and a short interdomain separation. Biochemistry (1998) 37:3612-3622.
25. GARDSVOLL H, DANO K, PLOUG M: Mapping part of the functional epitope for ligand binding on the receptor for urokinase-type plasminogen activator by site-directed mutagenesis. J. Biol. Chem. (1999) 274:37995-38003.
26. BDEIR K, KUO A, MAZAR A et al.: A region in domain II of the urokinase receptor required for urokinase binding. J. Biol. Chem. (2000) 275:28532-28538.
27. ENGELHOM LH, BEHRENDT N: Differential binding of urokinase and peptide antagonists to the urokinase receptor evidence from characterisation of the receptor in four primate species. Biol. Chem. (2001) 382:435-442.
28. NAR H, BAUER M, STASSEN JM et al.: Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation. J. Mol. Biol. (2000) 297:683-695.
29. SEIFFERT D, CIAMBRONE G, WAGNER NV, BINDER BR, LOSKUTOFF DJ: The somatomedin B domain of vitronectin. Structural requirements for the binding and stabilisation of active Type 1 plasminogen activator inhibitor. J. Biol. Chem. (1994) 269:2659-2666.
30. LAWRENCE DA, PALANIAPPAN S, STEFANSSON S et al.: Characterisation of the binding of different conformational forms of plasminogen activator inhibitor-1 to vitronectin. Implications for the regulation of pericellular proteolysis. J. Biol. Chem. (1997) 272:7676-7680.
31. WEI Y, WALTZ DA, RAO N et al.: Identification of the urokinase receptor as an adhesion receptor for vitronectin. J. Biol. Chem. (1994) 269:32380-32388.
32. DENG G, CURRIDEN SA, WANG S, ROSENBERG S, LOSKUTOFF D: Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J. Cell Biol. (1996) 134:1563-1571.
33. DENG G, ROYLE G, WANG S, CRAIN K, LOSKUTOFF D: Structural and function analysis of the plasminogen activator inhibitor-1 binding motif in the somatomedin B domain of vitronectin. J. Biol. Chem. (1996) 271:12716-12723.
34. KANSE SM, KOST C, WILHELM OG, ANDREASEN PA, PREISSNER KT: The urokinase receptor is a major vitronectin-binding protein on endothelial cells. Exp. Cell Res. (1996) 224:344-353.
35. KJOLLER L, HALL A: Rac mediates cytoskeletal rearrangements and increased cell motility induced by urokinase-type plasminogen activator receptor binding to vitronectin. J. Cell Biol. (2001) 152:1145-1157.
36. 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.
37. CZEKAY RP, KUEMMEL TA, ORLANDO RA, FARQUHAR MG: Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity. Mol. Biol. Cell (2001) 12:1467-1479.
38. SAKTHIVEL R, ZHANG JC, STRICKLAND DK, GAFVELS M, MCCRAE KR: Regulation of the ligand binding activity of the human very low density lipoprotein receptor by protein kinase C-dependent phosphorylation. J. Biol. Chem. (2001) 276:555-562.
39. NYKJAER A, CONESE M, CHRISTENSEN EI et al.: Recycling of the urokinase receptor upon internalisation of the uPA:serpin complexes. EMBO J. (1997) 16:2610-2620.
40. CHAPMAN HA: Plasminogen activators, integrins, and the co-ordinated regulation of cell adhesion and migration. Curr. Opin. Cell Biol. (1997) 9:714-724.
41. BOHUSLAV J, HOREJSI V, HANSMANN C et al.: Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes. J. Exp. Med. (1995) 181:1381-1390.
42. SIMON DI, RAO NK, XU H et al.: Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells. Blood (1996) 88:3185-3194.
43. WEI Y, LUKASHEV M, SIMON DI et al.: Regulation of integrin function by the urokinase receptor. Science (1996) 273:1551-1555.
44. CHAPMAN HA, WEI Y, SIMON DI, WALTZ D: Role of urokinase receptor and caveolin in regulation of integrin signalling. Thromb. Haemostasis (1999) 82:291-297.
45. SIMON DI, WEI Y, ZHANG L et al.: Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function. J. Biol. Chem. (2000) 275:10228-10234.
46. rd, PETTY HR: Urokinase-rype plasminogen activator receptors associate with beta1 and beta3 integrins of fibrosarcoma cells: dependence on extracellular matrix components. Cancer Res. (1997) 57:1682-1689.
47. GHOSH S, BROWN R, JONES JC, ELLERBROEK SM, STACK MS: Urinary-type plasminogen activator (uPA) expression and uPA receptor localisation are regulated by alpha 3 beta 1 integrin in oral keratinocytes. J. Biol. Chem. (2000) 275:23869-23876.
48. CARRIERO MV, DEL VECCHIO S, CAPOZZOLI M et al.: Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer. Cancer Res. (1999) 59:5307-5314.
49. YEBRA M, PARRY GC, STROMBLAD S et al.: Requirement of receptor-bound urokinase-type plasminogen activator for integrin alphavbeta5-directed cell migration. J. Biol. Chem. (1996) 271:29393-29399.
50. CHAPMAN HA, WEI Y: Protease crosstalk with integrins: the urokinase receptor paradigm. Thromb. Haemostasis (2001) 86:124-129.
51. SITRIN RG, PAN PM, BLACKWOOD RA, HUANG J, PETTY HR: Cutting edge: evidence for a signalling partnership between urokinase receptors (cd87) and L-selectin (cd62l) in human polymorphonuclear neutrophils. J. Immunol. (2001) 166:4822-4825.
52. ZHANG JC, CLAFFEY K, SAKTHIVEL R et al.: Two-chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5. FASEB J. (2000) 14:2589-2600.
53. CHAVAKIS T, KANSE SM, LUPU F et al.: Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions. Blood (2000) 96:514-522.
54. COLMAN RW, PIXLEY RA, NAJAMUNNISA S et al.: Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor. J. Clin. Invest. (1997) 100:1481-1487.
55. GODAR S, HOREJSI V, WEIDLE UH et al.: M6P/IGFII-receptor complexes urokinase receptor and plasminogen for activation of transforming growth factor-beta1. Eur. J. Immunol. (1999) 29:1004-1013.
56. 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. (1998) 141:815-828.
57. BEHRENDT N, JENSEN ON, ENGELHOLM LH et al.: A urokinase receptor-associated protein with specific collagen binding properties. J. Biol. Chem. (2000) 275:1993-2002.
58. ALBO D, ROTHMAN VL, ROBERTS DD, TUSZYNSKI GP: Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor. Br. J. Cancer (2000) 83:298-306.
59. AGUIRRE-GHISO JA, KOVALSKI K, OSSOWSKI L: Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signalling. J. Cell. Biol. (1999) 147:89-104.
60. AGUIRRE-GHISO JA, LIU D, MIGNATTI A, KOVALSKI K, OSSOWSKI L: Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol. Biol. Cell (2001) 12:863-879.
61. WALTZ DA, FUJITA RM, YANG X et al.: Nonproteolytic role for the urokinase receptor in cellular migration in vivo. Am. J. Resp. Cell. Mol. Biol. (2000) 22:316-322.
62. MAY AE, KANSE SM, LUND LR et al.: Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J. Exp. Med. (1998) 188:1029-1037.
63. FOEKENS JA, PETERS HA, LOOK MP et al.: The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res. (2000) 60:636-643.
64. ANDREASEN PA, KJOLLER L, CHRISTENSEN L, DUFFY MJ: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int. J. Cancer (1997) 72:1-22.
65. JANICKE F, PRECHTL A, THOMSSEN C et al.: 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.
66. BUGGE TH, KOMBRINCK KW, XIAO Q et al.: Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice. Blood (1997) 90:4522-4531.
67. BUGGE TH, LUND LR, KOMBRINCK KK et al.: Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice. Oncogene (1998) 16:3097-3104.
68. SHAPIRO RL, DUQUETTE JG, ROSES DF et al.: Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals. Cancer Res. (1996) 56:3597-3604.
69. TRESSLER RJ, PITOT PA, STRATTON JR et al.: Urokinase receptor antagonists: discovery and application to in vivo models of tumor growth. APMIS (1999) 107:168-173.
70. FRANDSEN TL, HOLST-HANSEN C, NIELSEN BS et al.: Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model. Cancer Res. (2001) 61:532-537.
71. BAJOU K, NOEL A, GERARD RD et al.: Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nature Med. (1998) 4:923-928.
72. BAJOU K, MASSON V, GERARD RD et al.: The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. J. Cell. Biol. (2001) 152:777-784.
73. GUTIERREZ LS, SCHULMAN A, BRITO-ROBINSON T et al.: Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res. (2000) 60:5839-5847.
74. MCMAHON GA, PETITCLERC E, STEFANSSON S et al.: Plasminogen activator inhibitor-1 regulates tumor growth and angiogenesis. J. Biol. Chem. (2001) 276:33964-33968.
75. STEFANSSON S, PETITCLERC E, WONG MK et al.: Inhibition of angiogenesis in vivo by plasminogen activator inhibitor-1. J. Biol. Chem. (2001) 276:8135-8141.
76. MIN HY, DOYLE LV, VITT CR et al.: Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res. (1996) 56:2428-2433.
77. LI H, GRISCELLI F, LINDENMEYER F et al.: Systemic delivery of antiangiogenic adenovirus AdmATF induces liver resistance to metastasis and prolongs survival of mice. Human Gene Ther. (1999) 10:3045-3053.
78. DEL ROSSO M, FIBBI G, MATUCCICERINIC M: The urokinase-type plasminogen activator system and inflammatory joint diseases. Clin. Exp. Rheumatol. (1999) 17:485-498.
79. YANG YH, CARMELIET P, HAMILTON JA: Tissue-type plasminogen activator deficiency exacerbates arthritis. J. Immunol. (2001) 167:1047-1052.
80. SIDENIUS N, SIER CF, ULLUM H et al.: Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection. Blood (2000) 96:4091-4095.
81. WADA M, WADA NA, SHIRONO H et al.: Amino-terminal fragment of urokinase-type plasminogen activator inhibits HIV-1 replication. Biochem. Biophys. Res. Commun. (2001) 284:346-351.
82. WILSON KJ, ILLIG CR, SUBASINGHE N et al.: Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors. Bioorg. Med. Chem. Lett. (2001) 11:915-918.
83. KLINGHOFER V, STEWART K, MCGONIGAL T et al.: Species specificity of amidine-based urokinase inhibitors. Biochemistry (2001) 40:9125-9131.
84. KRUGER A, SOELTL R, LUTZ V et al.: Reduction of breast carcinoma tumor growth and lung colonization by overexpression of the soluble urokinase-type plasminogen activator receptor (CD87). Cancer Gene Ther. (2000) 7:292-299.
85. VAN DER LAAN WH, PAP T, RONDAY HK et al.: Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of a cell surface-targeted plasmin inhibitor. Arthritis Rheum. (2000) 43:1710-1718.
86. QUAX PH, LAMFERS ML, LARDENOYE JH et al.: Adenoviral expression of a urokinase receptor-targeted protease inhibitor inhibits neointima formation in murine and human blood vessels. Circulation (2001) 103:562-569.
87. KOBAYASHI H, SUGINO D, SHE MY et al.: A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and domain II of bikunin efficiently inhibits tumor cell invasion and metastasis. Eur. J. Biochem. (1998) 253:817-826.
88. YU W, KIM J OSSOWSKI L: Reduction in surface urokinase receptor forces malignant cells into a protracted state of dormancy. J. Cell. Biol. (1997) 137:767-777.
89. DEL ROSSO M, FIBBI G, PUCCI M, CERINIC MM: Antisense oligonucleotides against the urokinase receptor: a therapeutic strategy for the control of cell invasion in rheumatoid arthritis and cancer. Clin. Exp. Rheumatol. (1998) 16:389-393.
90. NGO TH, HOYLAERTS MF, KNOCKAERT I, BROUWERS E, DECLERCK PJ: Identification of a target-site in plasminogen activator inhibitor-1 that allows neutralization of its inhibitory properties concomitant with an allosteric upregulation of its anti-adhesive properties. J. Biol. Chem. (2001) 276:26243-26248.
91. CHAPPUIS PO, DIETERICH B, SCIRETTA V et al.: Functional evaluation of plastnin formation in primary breast cancer. J. Clin. Oncol. (2001) 19:2731-2738.
92. PEDERSEN AN, CHRISTENSEN IJ, STEPHENS RW et al.: The complex between urokinase and its type-1 inhibitor in primary breast cancer: relation to survival. Cancer Res. (2000) 60:6927-6934.
93. WEBB DJ, THOMAS KS, GONIAS SL: Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signalling and thereby promotes MCF-7 cell growth. J. Cell. Biol. (2001) 152:741-752.
94. DEGRYSE B, RESNATI M, RABBANI SA et al.: Src-dependence and pertussis-toxin sensitivity of urokinase receptor-dependent chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. Blood (1999) 94:649-662.
95. RESNATI M, GUTTINGER M, VALCAMONICA S et al.: Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO. J. (1996) 15:1572-1582.
96. WEBB DJ, NGUYEN DH, GONIAS SL: Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion. J. Cell Sci. (2000) 113:123-134.
97. KOSHELNICK Y, EHART M, HUFNAGL P, HEINRICH PC, BINDER BR: Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598. J. Biol. Chem. (1997) 272:28563-28567.
98. FIBBI G, CALDINI R, CHEVANNE M et al.: Urokinase-dependent angiogenesis in vitro and diacylglycerol production are blocked by antisense oligonucleotides against the urokinase receptor. Lab. Invest. (1998) 78:1109-1119.
99. KUSCH A, TKACHUK S, HALLER H et al.: Urokinase stimulates human vascular smooth muscle cell migration via a phosphatidylinositol 3-kinase-Tyk2 interaction. J. Biol. Chem. (2000) 275:39466-39473.
100. ABBOTT LABS: WO9905076 (1999).
101. ABBOTT LABS: US6207701 B1 (2001).
102. 3-DIMENSIONAL PHARM, INC.: WO9940088 (1999).
103. 3-DIMENSIONAL PHARM, INC.: WO9955355 (1999).
104. AXYS PHARM INC.: WO0035886 (2000).
105. PFIZER LTD.: WO9920608 (1999).
106. PFIZER LTD.: WO0005214 (2000).
107. PFIZER LTD.: EP-1044967 (2000).
108. PENTAPHARM AG: WO0017158 (2000).
109. WILEX BIOTECH GMBH: WO0004954 (2000).
110. CANCERFORSKNINGSFONDEN AF: US6248712B1 (2001).
111. CHIRON CORP.: WO9640747 (1996).
112. CHIRON CORP.: US5747458 (1998).
113. F HOFFMANN-LA ROCHE AG: WO9906387 (1999).
114. SCHERING-PLOUGH: US 6228985 (2001).
115. CHIRON CORP., BRIGHAM & WOMEN'S HOSPITAL INC.: WO9735969 (1997).
116. BRIGHAM AND WOMEN'S HOSPITAL INC.: WO 0117544A1 (2001).