The urokinase plasminogen activator and its receptor

Daniela Alfano; Paola Franco; Immacolata Vocca; Nadia Gambi; Viviana Pisa; Alessandro Mancini; Mario Caputi; Maria Vincenza Carriero; Ingram Iaccarino; Maria Patrizia Stoppelli

doi:10.1160/TH04-09-0592

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 93(02): 205-211
DOI: 10.1160/TH04-09-0592

Theme Issue Article

Schattauer GmbH

The urokinase plasminogen activator and its receptor

Role in cell growth and apoptosis

Daniela Alfano

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Paola Franco

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Immacolata Vocca

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Nadia Gambi

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Viviana Pisa

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Alessandro Mancini

²Department of Medical-Surgical, Cardiological, Respiratory, and Thoracic Sciences, Second University of Naples, Naples, Italy

,

Mario Caputi

²Department of Medical-Surgical, Cardiological, Respiratory, and Thoracic Sciences, Second University of Naples, Naples, Italy

,

Maria Vincenza Carriero

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

³National Cancer Institute of Naples, Naples, Italy

,

Ingram Iaccarino

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

,

Maria Patrizia Stoppelli

¹Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, Italy

› Institutsangaben

Abstract

Summary

The urinary-type plasminogen activator, or uPA, controls matrix degradation through the conversion of plasminogen into plasmin and is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis).The proteolytic activity of uPA is responsible for the activation or release of several growth factors and modulates the cell survival/apoptosis ratio through the dynamic control of cell-matrix contacts. The urokinase receptor (uPAR), binding to the EGF-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating cell migration, adhesion and cytoskeletal status. However, recent evidence highlights an intricate relationship linking the uPA/uPAR system to cell growth and apoptosis.

Keywords

Urokinase - urokinase receptor - cell proliferation - tumour progression - apoptosis

Volltext

Referenzen

References
1 Johnsen M, Lund LR, Romer J. et al Cancer invasion and tissue remodeling: common themes in proteolytic matrix degradation.. Curr Opin Cell Biol 1998; 10 (05) 667-71.
2 Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator.. Nat Rev Mol Cell Biol 2002; 03 (12) 932-43.
3 List K, Jensen ON, Bugge TH. et al Plasminogenindependent 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: 508-15.
4 Franco P, Iaccarino C, Chiaradonna F. et al Phosphorylation of pro-urokinase at Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adhesion and motility.. J Cell Biol 1997; 137: 779-91.
5 Camani C, Gavin O, Bertossa C. et al Studies on the effect of fucosylated and non-fucosylated finger/ growth-factor constructs on the clearance of tissuetype plasminogen activator mediated by the low-density- lipoprotein-receptor-related protein.. Eur J Biochem 1998; 251: 804-11.
6 Riccio A, Grimaldi G, Verde P. et al The human urokinase-plasminogen activator gene and its promoter.. Nucleic Acids Res 1985; 13 (08) 2759-71.
7 Irigoyen JP, Munoz-Canoves P, Montero L. et al The plasminogen activator system: biology and regulation.. Cell Mol Life Sci 1999; 56 1舑2 104-32.
8 Miralles F, Parra M, Caelles C. et al UV irradiation induces the murine urokinase-type plasminogen activator gene via the c-Jun N-terminal kinase signalling pathway: requirement of an AP1 enhancer element.. Mol Cell Biol 1998; 18 (08) 4537-47.
9 Watabe T, Yoshida K, Shindoh M. et al The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor.. Int J Cancer 1998; 77 (01) 128-37.
10 Han Q, Leng J, Bian D. et al Rac1-MKK3-p38-MAPKAPK2 pathway promotes urokinase plasminogen activator mRNA stability in invasive breast cancer cells.. J Biol Chem 2002; 277 (50) 48379-85.
11 Tran H, Maurer F, Nagamine Y. Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2.. Mol Cell Biol 2003; 23 (20) 7177-88.
12 Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase.. J Cell Biol 1985; 100 (01) 86-92.
13 Stoppelli MP, Corti A, Soffientini A. et al Differentiation- enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes.. Proc Natl Acad Sci U S A 1985; 82 (15) 4939-43.
14 Magdolen V, Rettenberger P, Koppitz M. et al Systematic mutational analysis of the receptor-binding region of the human urokinase-type plasminogen activator.. Eur J Biochem 1996; 237 (03) 743-51.
15 Simons K, Toomre D. Lipid rafts and signal transduction.. Nat Rev Mol Cell Biol 2000; 1 (01) 31-9.
16 Cunningham O, Andolfo A, Santovito ML. et al Dimerization controls the lipid raft partitioning of uPAR/ CD87 and regulates its biological functions.. EMBO J 2003; 22 (22) 5994-6003.
17 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: 5307-14.
18 Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator.. Nat Rev Mol Cell Biol 2002; 3 (12) 932-43.
19 Soravia E, Grebe A, De Luca P. et al A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene.. Blood 1995; 86 (02) 624-35.
20 Zannetti A, Del Vecchio S, Carriero MV. et al Salvatore M. Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma.. Cancer Res 2000; 60 (06) 1546-51.
21 Mazzieri R, Masiero L, Zanetta L. et al Control of type IV collagenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants.. EMBO J 1997; 16: 2319-32.
22 Carmeliet P, Moons L, Lijnen R. et al Urokinasegenerated plasmin activates matrix metalloproteinases during aneurysm formation.. Nat Genet 1997; 17 (04) 439-44.
23 Behrendt N. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling.. Biol Chem 2004; 385 (02) 103-36.
24 Rossignol P, Ho-Tin-Noe B, Vranckx R. et al Protease nexin-1 inhibits plasminogen activation-induced apoptosis of adherent cells.. J Biol Chem 2004; 279 (11) 10346-56.
25 Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation.. J Cell Sci 2003; 116 (Pt 2) 217-24.
26 Lund LR, Romer J, Bugge TH. et al Functional overlap between two classes of matrix-degrading proteases in wound healing.. EMBO J 1999; 18: 4645-56.
27 Zhang YW, Graveel C, Shinomiya N. et al Met decoys: will cancer take the bait?. Cancer Cell 2004; 6 (01) 5-6.
28 Ellis V, Behrendt N, Dano K. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor.. J Biol Chem 1991; 266 (19) 12752-8.
29 Andolfo A, English WR, Resnati M. et al Metalloproteases cleave the urokinase-type plasminogen activator receptor in the D1-D2 linker region and expose epitopes not present in the intact soluble receptor.. Thromb Haemost 2002; 88 (02) 298-306.
30 Sabapathy KT, Pepper MS, Kiefer F. et al Polyoma middle T-induced vascular tumor formation: the role of the plasminogen activator/plasmin system.. J Cell Biol 1997; 137 (04) 953-63.
31 Devy L, Blacher S, Grignet-Debrus C. et al The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent.. FASEB J 2002; 16 (02) 147-54.
32 Zhou HM, Nichols A, Meda P. et al Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis.. EMBO J 2000; 19 (17) 4817-26.
33 Ikeo K, Takahashi K, Gojobori T. Different evolutionary histories of kringle and protease domains in serine proteases: a typical example of domain evolution.. J Mol Evol 1995; 40 (03) 331-6.
34 Patthy L. Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules.. Cell 1985; 41 (03) 657-63.
35 Kim KS, Hong YK, Joe YA. et al Anti-angiogenic activity of the recombinant kringle domain of urokinase and its specific entry into endothelial cells.. J Biol Chem 2003; 278 (13) 11449-56.
36 Mukhina S, Stepanova V, Traktouev D. et al The chemotactic action of urokinase on smooth muscle cells is dependent on its kringle domain. Characterization of interactions and contribution to chemotaxis.. J Biol Chem 2000; 275 (22) 16450-8.
37 Liang OD, Chavakis T, Linder M. et al Binding of urokinase plasminogen activator to gp130 via a putative urokinase-binding consensus sequence.. Biol Chem 2003; 384 (02) 229-36.
38 Bdeir K, Kuo A, Sachais BS. et al The kringle stabilizes urokinase binding to the urokinase receptor.. Blood 2003; 102 (10) 3600-8.
39 Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership: coordination of signalling for cell adhesion, migration and growth.. Curr Opin Cell Biol 2000; 12 (05) 613-20.
40 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: 5307-14.
41 Liu D, Aguirre Ghiso J, Estrada Y. et al EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma.. Cancer Cell 2002; 1 (05) 445-57.
42 Preissner KT, Kanse SM, May AE. Urokinase receptor: a molecular organizer in cellular communication.. Curr Opin Cell Biol 2000; 12 (05) 621-8.
43 Chiaradonna F, Fontana L, Iavarone C. et al Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence.. EMBO J 1999; 18 (11) 3013-23.
44 Kirchheimer JC, Wojta J, Christ G. et al Functional inhibition of endogenously produced urokinase decreases cell proliferation in a human melanoma cell line.. Proc Natl Acad Sci U S A 1989; 86: 5424-8.
45 Fischer K, Lutz V, Wilhelm O. et al Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function.. FEBS Lett 1998; 438 1–2 101-5.
46 Kanse SM, Benzakour O, Kanthou C. et al Induction of vascular SMC proliferation by urokinase indicates a novel mechanism of action in vasoproliferative disorders.. Arterioscler Thromb Vasc Biol 1997; 17: 2848-54.
47 Koopman JL, Slomp J, de Bart AC. et al Mitogenic effects of urokinase on melanoma cells are independent of high affinity binding to the urokinase receptor.. J Biol Chem 1998; 273 (50) 33267-72.
48 Rabbani SA, Mazar AP, Bernier SM. et al Structural requirements for the growth factor activity of the amino-terminal domain of urokinase.. J Biol Chem 1992; 267 (20) 14151-6.
49 Kook YH, Adamski J, Zelent A. et al The effect of antisense inhibition of urokinase receptor in human squamous cell carcinoma on malignancy.. EMBO 1994; 13 (17) 3983-91.
50 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 (03) 767-77.
51 Aguirre-Ghiso JA, Liu D, Mignatti A. et al 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 (04) 863-79.
52 Aguirre Ghiso JA. Inhibition of FAK signalling activated by urokinase receptor induces dormancy in human carcinoma cells in vivo.. Oncogene 2002; 21 (16) 2513-24.
53 Liu D, Aguirre Ghiso JA., Estrada Y. et al EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma.. Cancer Cell 2002; 1: 445-457.
54 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: 3597-604.
55 Gyetko MR, Sud S, Chen GH. et al Urokinasetype plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection.. J Immunol 2002; 168 (02) 801-9.
56 Herbert JM, Lamarche I, Carmeliet P. Urokinase and tissue-type plasminogen activator are required for the mitogenic and chemotactic effects of bovine fibroblast growth factor and platelet-derived growth factor- BB for vascular smooth muscle cells.. J Biol Chem 1997; 272 (38) 23585-91.
57 Suelves M, Lopez-Alemany R, Lluis F. et al Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivo.. Blood 2002; 99 (08) 2835-44.
58 Roselli HT, Su M, Washington K. et al Liver regeneration is transiently impaired in urokinase-deficient mice.. Am J Physiol 1998; 275 6Pt 1 G1472-9.
59 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 (20) 5839-47.
60 Yanamandra N, Konduri SD, Mohanam S. et al Downregulation of urokinase-type plasminogen activator receptor (uPAR) induces caspase-mediated cell death in human glioblastoma cells.. Clin Exp Metastasis 2000; 18 (07) 611-5.
61 Krishnamoorthy B, Darnay B, Aggarwal B. et al Glioma cells deficient in urokinase plaminogen activator receptor expression are susceptible to tumor necrosis factor-alpha-related apoptosis-inducing ligandinduced apoptosis.. Clin Cancer Res 2001; 7 (12) 4195-201.
62 Ma Z, Webb DJ, Jo M. et al Endogenously produced urokinase-type plasminogen activator is a major determinant of the basal level of activated ERK/MAP kinase and prevents apoptosis in MDA-MB-231 breast cancer cells.. J Cell Sci 2001; 114 Pt 18 3387-96.
63 Chandrasekar N, Mohanam S, Gujrati M. et al Downregulation of uPA inhibits migration and PI3k/Akt signalling in glioblastoma cells.. Oncogene 2003; 22 (03) 392-400.
64 Cheng EH, Wei MC, Weiler S. et al BCL-2, BCLX( L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.. Mol Cell 2001; 8: 705-11.
65 Wick W, Wagner S, Kerkau S. et al BCL-2 promotes migration and invasiveness of human glioma cells.. FEBS Lett 1998; 440 (03) 419-24.
66 Trisciuoglio D, Iervolino A, Candiloro A. et al bcl-2 induction of urokinase plasminogen activator receptor expression in human cancer cells through Sp1 activation: involvement of ERK1/ERK2 activity.. J Biol Chem 2004; 279 (08) 6737-45.
67 Barnhart BC, Legembre P, Pietras E. et al CD95 ligand induces motility and invasiveness of apoptosisresistant tumour cells.. EMBO J 2004; 23: 3175-85.
68 Hanahan D, Weinberg RA. The hallmarks of cancer.. Cell 2000; 100 (01) 57-70.
69 Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E. et al Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB.. Nature 1997; 385 6616 544-8.
70 Frisch SM, Francis H. Disruption of epithelial cellmatrix interactions induces apoptosis.. J Cell Biol 1994; 124 (04) 619-26.
71 Lund AH, Turner G, Trubetskoy A. et al Genomewide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice.. Nat Genet 2002; 32 (01) 160-5.
72 Romer J, Nielsen BS, Ploug M. The urokinase receptor as a potential target in cancer therapy.. Curr Pharm Des 2004; 10 (19) 2359-76.
73 Rabbani SA, Gladu J. Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo.. Cancer Res 2002; 62 (08) 2390-7.
74 Sato S, Kopitz C, Schmalix WA. et al High-affinity urokinase-derived cyclic peptides inhibiting urokinase/ urokinase receptor-interaction: effects on tumor growth and spread.. FEBS Lett 2002; 528 1–3 212-6.
75 Fabbrini MS, Carpani D, Bello-Rivero I. et al The amino-terminal fragment of human urokinase directs a recombinant chimeric toxin to target cells: internalization is toxin mediated.. FASEB J 1997; 11 (13) 1169-76.
76 Adachi Y, Chandrasekar N, Kin Y. et al Suppression of glioma invasion and growth by adenovirus-mediated delivery of a bicistronic construct containing antisense uPAR and sense p16 gene sequences.. Oncogene 2002; 21 (01) 87-95.
77 Bu X, Khankaldyyan V, Gonzales-Gomez I. et al Species-specific urokinase receptor ligands reduce glioma growth and increase survival primarily by an antiangiogenesis mechanism.. Lab Invest 2004; 84 (06) 667-78.
78 Pakneshan P, Szyf M, Farias-Eisner R. et al Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis.. J Biol Chem 2004; 279 (30) 31735-44.
79 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: 10228-34.
80 Franco P, Massa O, Garcia-Rocha M. et al Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist.. J Biol Chem 1998; 273: 27734-40.
81 Guo Y, Higazi AA, Arakelian A. et al A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.. FASEB J 2000; 14: 1400-10.
82 Mishima K, Mazar AP, Gown A. et al A peptide derived from the non-receptor-binding region of urokinase plasminogen activator inhibits glioblastoma growth and angiogenesis in vivo in combination with cisplatin.. Proc Natl Acad Sci U S A 2000; 97: 8484-9.