Molecular interactions involving urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), as new targets for tumour therapy
Frankenne, F.; Noël, Agnès; Bajou, Khalidet al.
1999 • In Expert Opinion on Therapeutic Targets, 3 (3), p. 469-481 (13
[en] In the promotion of cancer progression, a classical role had previously been ascribed to the plasminogen activation system on the basis of urokinase plasminogen activator (uPA) proteolytic activity and plasminogen activation triggering a focalised pericellular activation cascade involving matrix metalloproteinases (MMPs). As a result, many pharmaceutical companies have undertaken the development of synthetic uPA inhibitors. However, during the last few years, data have accumulated that uPA, as well as urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are likely to play an essential role in tumour progression through non-proteolysis-related activities. Such activities endow them with new and likely key functions in tumour progression-associated events, such as cellular adhesion, migration, invasion and angiogenesis. Since these activities essentially depend upon protein-protein interactions, they represent new therapeutic targets.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Frankenne, F.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Bajou, Khalid ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Sounni, Nor Eddine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Remacle, A.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Language :
English
Title :
Molecular interactions involving urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), as new targets for tumour therapy
HEISS MM, ALLGAYER H, GRUETZNER KU et al.: Individual development and uPA-receptor expression of disseminated tumour cells in bone marrow: a reference to early systemic disease in solid cancer. Nature Med. (1995) 1:1035-1039.
SCHMITT M, HARBECK N, THOMSSEN C et al.: Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb. Haemost. (1997) 78:285-296. (Pubitemid 27289256)
REUNING U, MAGDOLEN V, WILHELM Oet al.: Multifunctional potential of the plasminogen activation system in tumor invasion and metastasis (review). Int. J. Oncol. (1998) 13:893-906. (Pubitemid 28506055)
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. (Pubitemid 27314632)
FESTUCCIA C, DOLO V, GUERRA F et al.: Plasminogen activator system modulates invasive capacity and proliferation in prostatic tumor cells. Clin. Exp. Metastasis (1998) 16:513-528. (Pubitemid 29009587)
CONNOLLY JM, SUN XG, ROSE DP: A comparison of the expression of the malignant phenotype in two androgeno-independent human prostate cancer cell lines after orthotopic implantation in nude mice. Int. J. Oncol. (1997) 11:771-776. (Pubitemid 27407955)
LYU MA, CHOI YK, PARK BN et al.: Over-expression of urokinase receptor in human epidermoid-carcinoma cell line (HEp3) increases tumorigenicity on chorioallantoic membrane and in severe-combinedimmunodeficient mice. Int. J. Cancer (1998) 77:257-263.
RABBANI SA, XING RH: Role of urokinase (uPA) and its receptor (uPAR) in invasion and metastasis of hormone-dependent malignancies. Int. J. Oncol. (1998) 12:911-920. (Pubitemid 28133587)
HAECKEL C, KRUEGER S, ROESSNER A: Antisense inhibition of urokinase: effect on malignancy in a human osteosarcoma cell line. Int. J. Cancer (1998) 77:153-160. (Pubitemid 28308565)
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. (Pubitemid 28364031)
STRANDBERG L, LAWRENCE D, NY T: The organization of the human-plasminogen-activator-inhibitor-1 gene. Implications on the evolution of the serine-protease inhibitor family. Eur. J. Biochem. (1988) 176:609-616.
VAUGHAN DE: Plasminogen activator inhibitor-1: a common denominator in cardiovascular disease. J. Invest. Med. (1998) 46:370-376. (Pubitemid 128455006)
PANNEKOEK H, VEERMAN H, LAMBERS H et al.: Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. EMBO J. (1986) 5:2539-2544.
AERTGEERTS K, DE BONDT HL, DE RANTER C, DECLERCK PJ: A model of the reactive form of plasminogen activator inhibitor-1. J. Struct. Biol. (1994) 113:239-245.
DECLERCK PJ, DE MOL M, ALESSI MC et al.: Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J. Biol. Chem. (1988) 263:15454-15461.
SCHMITT M, WILHELM O, JANICKE F et al.: Urokinasetype plasminogen activator (uPA) and its receptor (CD87): a new target in tumor invasion and metastasis. J. Obstet. Gynaecol. (1995) 21:151-165.
ANDREASEN PA, SOTTRUP-JENSEN L, KJOLLER L et al.: Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes. FEBS Lett. (1994) 338:239-245. (Pubitemid 24056729)
RONNE E, BEHRENDT N, ELLIS V, PLOUG M, DANO K, HOYER-HANSEN G: Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor. FEBS Lett. (1991) 288:233-236.
PLOUG M, OSTERGAARD S, HANSEN LB, HOLM A, DANO K: Photoaffinity labeling 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. (Pubitemid 28162916)
WALTZ DA, CHAPMAN HA: Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy. J. Biol. Chem. (1994) 269:14746-14750. (Pubitemid 24194041)
CHAVAKIS T, KANSE SM, YUTZY B, LIJNEN HR, PREISSNER KT: Vitronectin concentrates proteolytic activity on the cell surface and extracellular matrix by trapping soluble urokinase receptor-urokinase complexes. Blood (1998) 91:2305-2312. (Pubitemid 28155503)
NYKJAER A, CONESE M, CHRISTENSEN EI et al.: Recycling of the urokinase receptor upon internalization of the uPA:serpin complexes. EMBO J. (1997) 16:2610-2620. (Pubitemid 27226200)
KRUITHOF EK, TRAN-THANG C, RANSIJN A, BACHMANN F: Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood (1984) 64:907-913. (Pubitemid 14003614)
SEIFFERT D, LOSKUTOFF DJ: Kinetic analysis of the interaction between Type 1 plasminogen activator inhibitor and vitronectin and evidence that the bovine inhibitor binds to a thrombin-derived amino-terminal fragment of bovine vitronectin. Biochim. Biophys. Acta (1991) 1078:23-30.
DENG G, ROYLE G, SEIFFERT D, LOSKUTOFF DJ: The PAI-1/vitronectin interaction: two cats in a bag? Thromb. Haemost. (1995) 74:66-70.
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. (Pubitemid 26330833)
EHRLICH HJ, GEBBINK RK, KEIJER J, PANNEKOEK H: Elucidation of structural requirements on plasminogen activator inhibitor 1 for binding to heparin. J. Biol. Chem. (1992) 267:11606-11611.
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. (Pubitemid 28217924)
BARAMOVA EN, BAJOU K, REMACLE A et al.: Involvement of PA/plasmin system in the processing of pro-MMP-9 and in the second step of pro-MMP-2 activation. FEBS Lett. (1997) 405:157-162. (Pubitemid 27136502)
STEPANOVA V, BOBIK A, BIBILASHVILY R et al.: Urokinase plasminogen activator induces smooth muscle cell migration: key role of growth factor-like domain. FEBS Lett. (1997) 414:471-474. (Pubitemid 27389419)
PEPPER MS, MONTESANO R, MANDRIOTA SJ, ORCI L, VASSALLI JD: Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis. Enzyme Protein (1996) 49:138-162. (Pubitemid 26181743)
CARMELIET P, MOONS L, DEWERCHIN M et al.: Insights in vessel development and vascular disorders using targeted inactivation and transfer of vascular endothelial growth factor, the tissue factor receptor, and the plasminogen system. Ann. NY Acad. Sci. (1997) 811:191-206. (Pubitemid 27308328)
WEI Y, LUKASHEV M, SIMON DI et al.: Regulation of integrin function by the urokinase receptor. Science (1996) 273:1551-1555. (Pubitemid 26301666)
DENG G, CURRIDEN SA, WANG S, ROSENBERG S, LOSKUTOFF DJ: Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J. Cell Biol. (1996) 134:1563-1571. (Pubitemid 26318027)
OKADA SS, GROBMYER SR, BARNATHAN ES: Contrasting effects of plasminogen activators, urokinase receptor, and LDL receptor-related protein on smooth muscle cell migration and invasion. Arterioscler. Thromb. Vasc. Biol. (1996) 16:1269-1276. (Pubitemid 26339715)
NGUYEN DH, HUSSAINI IM, GONIAS SL: Binding of urokinase-type plasminogen activator to its receptor in MCF-7 cells activates extracellular signal-regulated kinase 1 and 2 which is required for increased cellular motility. J. Biol. Chem. (1998) 273:8502-8507. (Pubitemid 28168915)
YEBRA M, PARRY GCN, STROMBLAD S et al.: Requirement of receptor-bound urokinase-type plasminogen activator for integrin avb5-directed cell migration. J. Biol. Chem. (1996) 271:29393-29399. (Pubitemid 26382657)
CAVALLARO U, WU Z, DI PALO A et al.: FGF-2 stimulates migration of Kaposi's sarcoma-like vascular cells by HGF-dependent relocalization of the urokinase receptor. FASEB J. (1998) 12:1027-1034. (Pubitemid 28359584)
BLASI F: uPA, uPAR, PAI-1: key intersection of proteolytic, adhesive and chemotactic highways? Immunol. Today (1997) 18:415-417. (Pubitemid 127773672)
MIRSHAHI SS, LOUNES KC, LU H et al.: Defective cell migration in an ovarian cancer cell line is associated with impaired urokinase-induced tyrosine phosphorylation. FEBS Lett. (1997) 411:322-326. (Pubitemid 27301478)
RESNATI M, GUTTINGER M, VALCAMONICA S, SIDENIUS N, BLASI F, FAZIOLI F: Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO J. (1996) 15:1572-1582. (Pubitemid 26112379)
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.
VAN DER BURG ME, HENZEN-LOGMANS SC, BERNS EM, VAN PUTTEN WL, KLIJN JG, FOEKENS JA: Expression of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in benign, borderline, malignant primary and metastatic ovarian tumors. Int. J. Cancer (1996) 69:475-479. (Pubitemid 27050525)
BLASI F: The urokinase receptor. A cell surface, regulated chemokine. APMIS (1999) 107:96-101. (Pubitemid 29133528)
LANG IM, MOSER KM, SCHLEEF RR: Elevated expression of urokinase-like plasminogen activator and plasminogen activator inhibitor Type 1 during the vascular remodeling associated with pulmonary thromboembolism. Arterioscler. Thromb. Vasc. Biol. (1998) 18:808-815. (Pubitemid 28267662)
TAKAHASHI K, UWABE Y, SAWASAKI Y et al.: Increased secretion of urokinase-type plasminogen activator by human lung microvascular endothelial cells. Am. J. Physiol. (1998) 275:L47-L54.
NAKATA S, ITO K, FUJIMORI M et al.: Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers. Int. J. Cancer (1998) 79:179-186. (Pubitemid 28201691)
OLOFSSON B, KORPELAINEN E, PEPPER MS et al.: Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc. Natl. Acad. Sci. USA (1998) 95:11709-11714. (Pubitemid 28460479)
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).272:23585-23591. (Pubitemid 27410929)
IWASAKA C, TANAKA K, ABE M, SATO Y: Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells. J. Cell Physiol. (1996) 169:522-531. (Pubitemid 26426918)
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. (Pubitemid 26154094)
FOLKMAN J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med. (1995) 1:27-31.
SANDBERG T, CASSLEN B, GUSTAVSSON B, BENRAAD TJ: Human endothelial cell migration is stimulated by urokinase plasminogen activator: plasminogen activator inhibitor 1 complex released from endometrial stromal cells stimulated with transforming growth factor 1; possible mechanism for paracrine stimulation of endometrial angiogenesis. Biol. Reprod. (1998) 59:759-767. (Pubitemid 28463325)
ALONSO DF, TEJERA AM, FARIAS EF, JOFFE EB, GOMEZ DE: Inhibition of mammary tumor cell adhesion, migration, and invasion by the selective synthetic urokinase inhibitor. Anticancer Res. (1998) 18:4499-4504. (Pubitemid 29043683)
IGNAR DM, ANDREWS JL, WITHERSPOON SM et al.: Inhibition of establishment of primary and micrometastatic tumors by a urokinase plasminogen activator receptor antagonist. Clin. Exp. Metastasis (1998) 16:9-20. (Pubitemid 28122551)
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. (Pubitemid 29133537)
LI H, LU H, GRISCELLI F et al.: Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice. Gene Ther. (1998) 5:1105-1113. (Pubitemid 28401313)
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. (Pubitemid 28223553)
