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CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review

Leukemia volume 18, pages 394–400 (2004)Cite this article

Abstract

The analysis of CD87 (urokinase-type plasminogen activator receptor – uPAR) expression has a potential role in the diagnostic or prognostic work-up of several hematological malignancies, particularly acute leukemia and multiple myeloma. The distribution of CD87 in acute myeloid leukemia (AML) varies according to the FAB subtype (highest expression in M5 and lowest in M0). Functionally, it is conceivable that the expression of CD87 could contribute to the invasive properties of the leukemic cells towards the skin and mucosal tissues as reflected by the clinical behavior of CD87 high cases. The lack of or weaker expression of CD87 on blast cells from ALL patients supports the concept that CD87 investigation might help in the distinction of AMLs from lymphoid malignancies. Among lymphoproliferative disorders, the expression of CD87 is exclusively found in pathological plasma cells. Since plasma cells also coexpress some adhesion molecules such as CD138 and CD56, this observation is consistent with the capacity of these cells to home in the bone compartment. High levels of soluble uPAR appear to represent an independent factor predicting worse prognosis and extramedullary involvement in multiple myeloma.

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References

  1. Bu G, Warshawsky I, Schwartz AL . Cellular receptors for the plasminogen activators. Blood 1994; 83: 3427–3436.

    CAS  PubMed  Google Scholar 

  2. Plesner T, Behrendt N, Ploug M . Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR. Stem Cells 1997; 15: 398–408.

    Article  CAS  Google Scholar 

  3. Wei Y, Lukashev M, Simon DJ, Bodary SC, Rosenberg S, Doyle MV et al. Regulation of integrin function by the urokinase receptor. Science 1996; 273: 1551–1555.

    Article  CAS  Google Scholar 

  4. Chapman HA . Plasminogen activators, integrins, and the co-ordinated regulation of cell adhesion and migration. Curr Opin Cell Biol 1997; 9: 714–724.

    Article  CAS  Google Scholar 

  5. May AE, Kanse SM, Lund LR, Gisler RH, Imhof BA, Preissner KT . Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 1998; 188: 1029–1037.

    Article  CAS  Google Scholar 

  6. Blasi F . Proteolysis, cell adhesion, chemotaxis and invasiveness are regulated by the uPA–uPAR–PAI1 system. Thromb Haemostasis 1999; 82: 298–304.

    Article  CAS  Google Scholar 

  7. Blasi F, Carmeliet P . uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3: 932–943.

    Article  CAS  Google Scholar 

  8. Petersen LC . Kinetics of pro-urokinase/plasminogen activation: stimulation by a template formed by the urokinase receptor bound to poly-D-lysine. Eur J Biochem 1997; 245: 316–323.

    Article  CAS  Google Scholar 

  9. Wei Y, Waltz DA, Rao N, Drummond RJ, Rosemberg S, Chapman HA . Identification of urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem 1994; 269: 32380–32388.

    CAS  Google Scholar 

  10. Pollanen J, Hedman K, Nielsen LS, Dano K, Vaheri A . Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol 1988; 106: 87–95.

    Article  CAS  Google Scholar 

  11. Sitrin RG, Pan PM, Harper HA, Todd III RF, Harsh DM, Blackwood RA . Clustering of urokinase receptors (uPAR; CD87) induces proinflammatory signalling in human polymorphonuclear neutrophils. J Immunol 2000; 165: 3341–3349.

    Article  CAS  Google Scholar 

  12. Fazioli F, Resnati M, Sidenius N, Higashimoto Y, Appella E, Blasi F . A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. EMBO J 1997; 16: 7279–7289.

    Article  CAS  Google Scholar 

  13. Gyetko M, Todd III R, Wilkinson C, Sitrin R . The urokinase receptor is required for monocyte chemotaxis in vitro. J Clin Invest 1994; 93: 2380–2388.

    Article  Google Scholar 

  14. Gyetko M, Sitrin R, Fuller J, Todd III R, Standiford T . Function of the urokinase receptor (CD87) in PMN chemotaxis. J Leukocyte Biol 1995; 58: 533–538.

    Article  CAS  Google Scholar 

  15. Wei Y, Yang X, Liu Q, Wilkins JA, Chapman H . A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signalling. J Cell Biol 1999; 144: 1285–1294.

    Article  CAS  Google Scholar 

  16. Wei Y, Eble JA, Wang Z, Kreidberg JA, Chapman HA . Urokinase receptors promote beta-1 integrin function through interactions with integrin alpha3beta1. Mol Biol Cell 2001; 12: 2975–2986.

    Article  CAS  Google Scholar 

  17. Mondino A, Resnati M, Blasi F . Structure and functions of the urokinase receptor. Thromb Haemostasis 1999; 82 (Suppl): 19–22.

    Google Scholar 

  18. Chapman HA, Wei Y, Simon D, Waltz DA . Role of urokinase receptor and caveolin in regulation of integrin signaling. Thromb Haemostasis 1999; 82: 291–297.

    Article  CAS  Google Scholar 

  19. Tarui T, Mazar AP, Cines DB, Takada Y . Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell–cell interaction. J Biol Chem 2001; 276: 3983–3990.

    Article  CAS  Google Scholar 

  20. Hjertner O, Qvigstad G, Hjorth-Hansen H, Seidel C, Woodliff J, Epstein J et al. Expression of urokinase plasminogen activator and the urokinase plasminogen activator receptor in myeloma cells. Br J Haematol 2000; 109: 815–822.

    Article  CAS  Google Scholar 

  21. Werb Z, Mainardi CL, Vater CA, Harris ED . Endogenous activation of latent collagenase by rheumatoid synovial cells Evidence for a role of plasminogen activator. N Engl J Med 1977; 296: 1017–1023.

    Article  CAS  Google Scholar 

  22. Carmeliet P, Moons L, Lijnen R, Baes M, Lemaitre V, Tipping P et al. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet 1997; 17: 439–444.

    Article  CAS  Google Scholar 

  23. Barille S, Akoundi C, Collette M, Mellerin MP, Rapp MJ, Harousseau JL et al. Metalloproteinases in multiple myeloma: production of matrix metalloproteinase-9 (MMP-9), activation of proMMP-2, and induction of MMP-1 by myeloma cells. Blood 1997; 90: 1649–1655.

    CAS  PubMed  Google Scholar 

  24. Daci E, Udagawa N, Martin TJ, Bouillon R, Carmeliet G . The role of the plasminogen system in bone resorption in vitro. J Bone Min Res 1999; 14: 946–952.

    Article  CAS  Google Scholar 

  25. Borset M, Hjorth-Hansen H, Seidel C, Sundan A, Waage A . Hepatocyte growth factor and its receptor c-met in multiple myeloma. Blood 1996; 88: 3998–4004.

    CAS  PubMed  Google Scholar 

  26. Hjertner O, Torgensen M, Seidel C, Hjotrh-Hansen H, Waage A, Borset M et al. Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease. Blood 1999; 94: 3883–3888.

    CAS  PubMed  Google Scholar 

  27. Pedersen N, Schmitt M, Ronne E, Nicoletti M, Hayer-Hansen G, Conese M et al. A ligand-free, soluble urokinase receptor is present in the ascitic fluid from patients with ovarian cancer. J Clin Invest 1993; 92: 2160–2167.

    Article  CAS  Google Scholar 

  28. Hoist-Hansen C, Hamers MJ, Johannessen BE, Brunner N, Stephens RW . Soluble urokinase receptor released from human carcinoma cells: a plasma parameter for xenograft tumour studies. Br J Cancer 1999; 81: 203–211.

    Article  Google Scholar 

  29. Sier CF, Stephens RW, Bizik J, Mariani A, Bassan M, Pedersen N et al. The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients. Cancer Res 1998; 58: 1843–1849.

    CAS  PubMed  Google Scholar 

  30. Stephens RW, Nielsen HJ, Christensen IJ, Sorensen S, Dano K, Brunner N . Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis. J Nat Cancer Inst 1999; 91: 869–874.

    Article  CAS  Google Scholar 

  31. Mustjoki S, Sidenius N, Sier CFM, Blasi F, Elonen E, Alitalo M et al. Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy. Cancer Res 2000; 60: 7126–7132.

    CAS  PubMed  Google Scholar 

  32. Riisbro R, Christensen IJ, Piironen T, Greenall M, Larsen B, Stephens RW et al. Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer. Clin Cancer Res 2002; 8: 1132–1141.

    PubMed  Google Scholar 

  33. Hoyer-Hansen G, Ronne E, Solberg H, Behrendt N, Ploug M, Lund LR . Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain. J Biol Chem 1992; 267: 18224–18229.

    CAS  PubMed  Google Scholar 

  34. Hoyer-Hansen G, Behrendt N, Ploug M, Dano K, Preissner KT . The intact urokinase receptor is required for efficient vitronectin binding: receptor cleavage prevents ligand interaction. FEBS Lett 1997; 420: 79–85.

    Article  CAS  Google Scholar 

  35. Wilhelm OG, Wilhelm S, Escott GM, Lutz V, Magdolen V, Schmitt M et al. Cellular glycosylphosphatidylinositol-specific phospholipase D regulates urokinase receptor shedding and cell surface expression. J Cell Physiol 1999; 180: 225–235.

    Article  CAS  Google Scholar 

  36. Blasi F . uPA, uPAR, PA-1: key interaction of proteolytic, adhesive, and chemotactic highways? Immunol Today 1997; 18: 415–417.

    Article  CAS  Google Scholar 

  37. Mizukami IF, Todd III RF . A soluble form of the urokinase plasminogen activator receptor (suPAR) can bind to hematopoietic cells. J Leukocyte Biol 1998; 64: 203–213.

    Article  CAS  Google Scholar 

  38. Todd III RF, Barnathan ES, Bohuslav J, Chapman HA, Cohen RL, Pelez J et al. CD87 cluster workshop report pp 932–9. In: Schlossman SF, Boumsell L, Gilks W, Harlan JM, Kishimoto T, Morimoto C, Ritz J, Shaw S, Silverstein R, Springer T, Tedder TF, Todd RF (eds) Leukocyte Typing V. White cell differentiation antigens. Proceedings of the Fifth international Workshop and Conference held in Boston USA 3–7 November 1993. Oxford, New York, Tokyo: Oxford University Press, 1995.

    Google Scholar 

  39. Béné MC, Castoldi GL, Knapp W, Ludwig WD, Matutes E, Orfao A et al. Proposals for the immunological classification of leukemias. Leukemia 1995; 9: 1783–1786.

    PubMed  Google Scholar 

  40. Lanza F, Castoldi GL, Castagnari B, Todd III RF, Moretti S, Spisani S et al. Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukemic cells. Br J Haematol 1998; 103: 110–123.

    Article  CAS  Google Scholar 

  41. Almeida J, Bueno C, Alguero MC, Sanchez ML, Canino MC, Fernandez ME et al. Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulation of normal human peripheral blood MHC+ lineage cells. Clin Exp Immunol 1999; 188: 392–409.

    Article  Google Scholar 

  42. Gadd S, Majdic O, Kasinrerk W, Stockinger H, Maurer D, Eher R et al. M5, a phosphoinositol linked human myelomonocytic activation associated antigen. Clin Exp Immunol 1990; 80: 252–256.

    Article  CAS  Google Scholar 

  43. Plesner T, Ralfkiaer E, Wittrup M, Johnsen H, Pyke C, Pedersen TL et al. Expression of the receptor for urokinase-type plasminogen activator in normal and neoplastic blood cells and hemopoietic tissue. Am J Clin Pathol 1994; 102: 835–841.

    Article  CAS  Google Scholar 

  44. Knapp W, Strobl H, Majdic O . Flow cytometric analysis of cell-surface and intracellular antigens in leukemia diagnosis. Cytometry 1994; 18: 187–198.

    Article  CAS  Google Scholar 

  45. Jard M, Ingles-Esteve J, Burgal M, Azqueta C, Velasco F, Lopez-Pedreira C et al. Distinct patterns of urokinase receptor (uPAR) expression by leukemic cells and peripheral blood cells. Thromb Haemostasis 1996; 76: 1009–1019.

    Article  Google Scholar 

  46. Mustjoki S, Alitalo R, Stephens RW, Vaheri A . Blast cell-surface and plasma soluble urokinase receptor in acute leukemia patients: relationship to classification and response to therapy. Thromb Haemostasis 1999; 81: 705–710.

    Article  CAS  Google Scholar 

  47. Lopez-Pedrera C, Jardì M, del Mar Malagon M, Ingles-Esteve J, Dorado G, Torres A et al. Tissue Factor (TF) and urokinase plasminogen activator receptor (uPAR) and bleeding complications in leukemic patients. Thromb Haemostasis 1997; 77: 62–70.

    Article  CAS  Google Scholar 

  48. Rigolin GM, Tieghi A, Ciccone M, Zenone Bragotti L, Cavazzini F, Della Porta M et al. Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra bone marrow involvement in multiple myeloma patients. Br J Haematol 2003; 120: 953–959.

    Article  CAS  Google Scholar 

  49. Hata H, Xiao H, Petrucci MT, Woodliff J, Chang R, Epstein J . Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells. Blood 1993; 81: 3357–3364.

    CAS  PubMed  Google Scholar 

  50. Schneider U, van Lessen A, Huhn D, Serke S . Two subsets of peripheral blood plasma cells defined by differential expression of CD45 antigen. Br J Haematol 1997; 97: 56–64.

    Article  CAS  Google Scholar 

  51. Rawstron A, Barrans S, Blythe D, Davies F, English A, Pratt G et al. Distribution of myeloma plasma cells in peripheral blood and bone marrow correlates with CD56 expression. Br J Haematol 1999; 104: 138–143.

    Article  CAS  Google Scholar 

  52. Yebra M, Goretzk L, Pfeifer M, Mueller BM . Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction. Exp Cell Res 1999; 250: 231–240.

    Article  CAS  Google Scholar 

  53. Kroon ME, Koolwijk P, Van Goor H, Weidle UH, Collen A, van der Pluijm G, van Hinsbergh VW . Role and localisation of urokinase receptor in the formation of new microvascular structures in fibrin matrices. Am J Pathol 1999; 154: 1731–1742.

    Article  CAS  Google Scholar 

  54. Koolwijk P, Sidenius N, Peters E, Sier CFM, Hanemaaijer R, Blasi F et al. Proteolysis of the urokinase-type plasminogen activator receptor by metallopoteinase-12: implication for angiogenesis in fibrin matrices. Blood 2001; 97: 3123–3131.

    Article  CAS  Google Scholar 

  55. Muehlenweg B, Sperl S, Magdolen V, Schmitt M, Harbeck N . Interference with the urokinase plasminogen activator system: a promising therapeutic concepts for solid tumor. Expert Opin Biol Ther 2001; 1: 683–691.

    Article  CAS  Google Scholar 

  56. Sato S, Kopitz C, Schmalix WA, Muehlenweg B, Kessler H, Schmitt M et al. High-affinity urokinase-derived cyclic peptides inhibiting urokinase/urokinase receptor-interaction: effects on tumor growth and spread. FEBS Lett 2002; 528: 212–216.

    Article  CAS  Google Scholar 

  57. Guo Y, Higazi AA, Arakelian A, Sachais BS, Cines D, Goldfarb RH 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. FASB J 2000; 14: 1400–1410.

    Article  CAS  Google Scholar 

  58. Frankel AE, Beran M, Hogge DE, Powell BL, Thorburn A, Chen YO et al. Malignant progenitors from patients with CD87+ acute myelogenous leukemia are sensitive to a diphtheria toxin-urokinase fusion protein. Exp Hematol 2002; 30: 1316–1323.

    Article  CAS  Google Scholar 

  59. Guo Y, Mazar AP, Lebrun JJ, Rabbani SA . An antiangiogenic urokinase-derived peptide combined with tamoxifen decreases tumor growth and metastasis in a syngenic model of breast cancer. Cancer Res 2002; 62: 4678–4684.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by MURST 60 and 40%, COFIN, AIRC coordinated project.

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Authors and Affiliations

  1. GEIL, Groupe d'Etude Immunologique des Leucémies, Immunology Laboratory, University Hospital of Nancy, Vandoeuvre les Nancy, France

    M C Béné

  2. Institute of Hematology, St Anna Hospital, Ferrara, Italy

    G Castoldi, G M Rigolin & F Lanza

  3. Institute of Immunology, University of Vienna, Vienna, Austria

    W Knapp

  4. Department of Hematology, Hospital Ramon y Cajal, Madrid, Spain

    L Escribano

  5. Department of Hematology and Blood Transfusion, Hospital Jihlava, Czech Republic

    P Lemez

  6. HELIOS Clinic Berlin, Robert Rössle Clinic, Charité, Humboldt-University, Berlin, Germany

    W-D Ludwig

  7. Department of Hematology, Royal Marsden Hospital, London, UK

    E Matutes

  8. Servicio de Citometria and Departamento de Medicina and Centro de Investigacion del Cancer, Hospital Universitario de Salamanca, Salamanca, Spain

    A Orfao

  9. Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands

    M van't Veer

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on behalf of EGIL, European Group on Immunological Classification of Leukemias

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Correspondence to G Castoldi.

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Béné, M., Castoldi, G., Knapp, W. et al. CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review. Leukemia 18, 394–400 (2004). https://doi.org/10.1038/sj.leu.2403250

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