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Urinbasierte Angiogenesemarker beim Urothelkarzinom der Harnblase

Urine-based markers of angiogenesis in bladder cancer

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Zusammenfassung

Angiogenese ist die Voraussetzung für Tumorwachstum und Metastasierung. Angiogenetisch wirksame Faktoren beim Harnblasenkarzinom, einer häufigen Erkrankung des Urogenitaltraktes, könnten neben diagnostisch und prognostisch informativen Werkzeugen, Ansatzpunkte für neue Therapie sein. Die Entwicklung weniger invasiver Techniken zur Diagnose und Prognoseabschätzung dieser Erkrankung, sowie die Bereitstellung einer individuelleren Therapie, hätte immense klinische Bedeutung. Für dieses wissenschaftliche Ziel ist die einfache Verfügbarkeit von Urin und Blut von Vorteil. Die wissenschaftlichen Bemühungen auf dem Gebiet der Angiogenese und Markersuche weiten sich aus. Die Methoden hierzu werden immer besser und präziser. Trotz kürzlicher Erfolge bei der Entwicklung antiangiogenetischer Therapieformen ist die Suche nach einem Marker oder einer Kombination von Markern, die die konventionelle Zystoskopienachsorge beim Harnblasenkarzinom ersetzten könnten, noch nicht abgeschlossen. Zu Recht werden jedoch weiterhin große Hoffnungen in solche Marker gesetzt.

Abstract

Angiogenesis is a prerequisite for tumour growth and metastasis. Therefore, angiogenesis factors in bladder cancer, a common disease of the genitourinary tract, could serve as diagnostic tools, predictors of prognosis, and targets for therapy. Development of less invasive or noninvasive detection techniques, reliable prognostic markers, and individualized targeted therapy would have a significant impact on disease management. For this investigative goal, the utility of urine and blood is beneficial. Research in the field of angiogenesis and promising markers is currently evolving. In spite of the recent success of antiangiogenic agents in the oncological clinic, an optimal marker that will warrant substitution of the cystoscopic follow-up protocol in patients with urothelial neoplasms has not been identified yet. Despite this challenge, allocating more resources and attention to identifying such urine markers is justified to optimize the diagnostics and follow-up of urinary bladder cancer.

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Literatur

  1. Boget S, Leriche A, Revol A (2001) Basic fibroblast growth factor and keratinocyte growth factor over-expression in benign prostatic hyperplasia. Farmaco 56(5–7):467–469

    Google Scholar 

  2. Cao Y, Langer R (2008) A review of judah folkman’s remarkable achievements in biomedicine. Proc Natl Acad Sci U S A 105(36):13203–13205 (Epub 2008 Sep 4)

    Article  PubMed  CAS  Google Scholar 

  3. Carmeliet P, Dor Y, Herbert JM et al (1998) Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394(6692):485–490

    Article  PubMed  CAS  Google Scholar 

  4. Cooksley CD, Avritscher EB, Grossman HB et al (2008) Clinical model of cost of bladder cancer in the elderly. Urologe A 71(3):519–525

    Google Scholar 

  5. Crew JP (1999) Vascular endothelial growth factor: An important angiogenic mediator in bladder cancer. Eur Urol 35:2–8

    Article  PubMed  CAS  Google Scholar 

  6. Daniely M, Rona R, Kaplan T et al (2007) Combined morphologic and fluorescence in situ hybridization analysis of voided urine samples for the detection and follow-up of bladder cancer in patients with benign urine cytology. Cancer 25(6):517–524

    Article  Google Scholar 

  7. Davis S, Aldrich TH, Jones PF et al (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87(7):1161–1169

    Article  PubMed  CAS  Google Scholar 

  8. Dickinson AJ, Fox SB, Persad RA et al (1994) Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br J Urol 74:762

    Article  PubMed  CAS  Google Scholar 

  9. vom Dorp F (2007) Combined cytology/cytometry for preventing misinterpretations of urine cytology. Urologe A 46(9):1140–1141

    Article  Google Scholar 

  10. Dosquet C, Coudert MC, Lepage E et al (1997) Are angiogenic factors, cytokines and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res 3:2451–2458

    PubMed  CAS  Google Scholar 

  11. Ergün S, Kilik N, Ziegeler G et al (2000) CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major effector of vascular endothelial growth factor. Mol Cell 5(2):311–320

    Article  PubMed  Google Scholar 

  12. Ferrara N, Davis-Smyth TD (1997) The biology of vascular endothelial growth factor. Endocr Rev 10:4

    Article  Google Scholar 

  13. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  PubMed  CAS  Google Scholar 

  14. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186

    PubMed  CAS  Google Scholar 

  15. Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29:15–18

    PubMed  CAS  Google Scholar 

  16. Folkman J, Merler E, Abernathy C, Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133:275–288

    Article  PubMed  CAS  Google Scholar 

  17. Fox SB, Gatter KC, Bicknell R et al (1993) Relationship of endothelial cell proliferation to tumor vascularity in human breast cancer. Cancer Res 53(18):4161–4163

    PubMed  CAS  Google Scholar 

  18. Goebell PJ, Groshen SL, Schmitz-Dräger BJ (2008) Guidelines for development of diagnostic markers in bladder cancer. World J Urol 26(1):5–11

    Article  PubMed  Google Scholar 

  19. Gravas S, Bosinakou I, Kehayas P, Giannopoulos A (2004) Urinary basic fibroblast growth factor in bladder cancer patients. Histopathological correlation and clinical potential. Urol Int 73(2):173–177

    Article  PubMed  CAS  Google Scholar 

  20. Gutiérrez Baños JL, Rebollo Rodrigo MH, Antolín Juárez FM, Martín García B (2001) NMP 22, BTA stat test and cytology in the diagnosis of bladder cancer: a comparative study. Urol Int 66(4):185–190

    Google Scholar 

  21. Hall MC, Troncoso P, Pollack A et al (1994) Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy. Urologe A 44:869

    CAS  Google Scholar 

  22. Herman MP, Svatek RS, Lotan Y et al (2008) Urine-based biomarkers for the early detection and surveillance of non-muscle invasive bladder cancer. Minerva Urol Nefrol 60(4):217–235

    PubMed  CAS  Google Scholar 

  23. Jaffe RB (2000) Importance of angiogenesis in reproductive physiology. Semin Perinatol 24:79–81

    Article  PubMed  CAS  Google Scholar 

  24. Jemal A, Siegel R, Ward E et al (2007) Cancer statistics. CA Cancer J Clin 57:43–66

    Article  PubMed  Google Scholar 

  25. Keck PJ, Hauser SD, Krivi G et al (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309

    Article  PubMed  CAS  Google Scholar 

  26. Kiemeney LA, Witjes JA, Verbeek AL et al (1993) The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. Br J Cancer 67:806–812

    PubMed  CAS  Google Scholar 

  27. Kilic N, Oliveira-Ferrer L, Wurmbach JH et al (2005) Pro-angiogenic signaling by the endothelial presence of CEACAM1. J Biol Chem 280(3):2361–2369

    Article  PubMed  CAS  Google Scholar 

  28. Leung DW, Cachianes G, Kuang W-J et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 86:1306

    Article  Google Scholar 

  29. Maisonpierre PC, Suri C, Jones PF et al (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322):55–60

    Article  PubMed  CAS  Google Scholar 

  30. Mandriota S, Montesano R, Orci L et al (1995) Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J Biol Chem 270:9709

    Article  PubMed  CAS  Google Scholar 

  31. Maxwell PH, Dachs GU, Gleadle JM et al (1997) Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci U S A 94(15):8104–8109

    Article  PubMed  CAS  Google Scholar 

  32. Nguyen M, Watanabe H, Budson AE et al (1994) Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 86(5):356–361

    Article  PubMed  CAS  Google Scholar 

  33. O’Brien T, Cranston D, Fuggle S et al (1997) Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder cancer. Cancer Res 57(1):136–140

    Google Scholar 

  34. Oka N, Yamamoto Y, Takahashi M et al (2005) Expression of angiopoietin-1 and -2, and its clinical significance in human bladder cancer. BJU Int 95(4):660–663

    Article  PubMed  CAS  Google Scholar 

  35. Park YS, Kim NH, Jo I (2003) Hypoxia and vascular endothelial growth factor acutely up-regulate angiopoietin-1 and Tie2 mRNA in bovine retinal pericytes. Microvasc Res 65(2):125–131

    Article  PubMed  CAS  Google Scholar 

  36. Patan S, Haenni B, Burri PH (1993) Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM). Anat Embryol (Berl) 187(2):121–130

    Google Scholar 

  37. Pepper MS, Ferrara N, Orci L, Montesano R (1991) Vascular endothelial growth factor induces plasminogen activators and plasminogen activator inhibitor-1 in micriovascular endothelial cells. Biochem Biophys Res Commun 181:902

    Article  PubMed  CAS  Google Scholar 

  38. Rifkin DB, Moscatelli D (1989) Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol 109(1):1–6

    Article  PubMed  CAS  Google Scholar 

  39. Scott PA, Harris AL (1994) Current approaches to targeting cancer using antiangiogenesis therapies. Cancer Treat Rev 20(4):393–412 Review

    Article  PubMed  CAS  Google Scholar 

  40. Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis fo 2596 patients from seven EORTC trials. Eur Urol 49:466–477 (discussion 475–477)

    Article  PubMed  Google Scholar 

  41. Szarvas T, Jäger T, Droste F et al (2008) Serum levels of angiogenic factors and their prognostic relevance in bladder cancer. Pathol Oncol Res (in press)

  42. Szarvas T, Jäger T, Tötsch M et al (2008) Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer. Clin Cancer Res 14(24):8253–8262

    Article  PubMed  CAS  Google Scholar 

  43. Tait CR, Jones PF (2004) Angiopoietins in tumours: the angiogenic switch. J Pathol 204(1):1–10

    Article  PubMed  CAS  Google Scholar 

  44. Takahashi A, Sasaki H, Kim S et al (1994) Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 54:4233

    PubMed  CAS  Google Scholar 

  45. Theodoropoulos VE, Lazaris AC, Kastriotis I et al (2005) Evaluation of hypoxia-inducible factor 1alpha overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma. BJU Int 95(3):425–431

    Article  PubMed  CAS  Google Scholar 

  46. Tilki D, Oliveira-Ferrer L, Kilic N et al (2007) One molecule, two faces. Epithelial loss of cell adhesion molecule CEACAM1 activates angiogenesis in bladder and prostate cancer. Urologe A 46(9):1128–1134

    Article  PubMed  CAS  Google Scholar 

  47. Unemori E, Ferrara N, Bauer E, Amento E (1992) Vascular endothelial growth factor induces institial collagenase expression in human enthelial cells. J Cell Physiol 153:557

    Article  PubMed  CAS  Google Scholar 

  48. Viglietto G, Romano A, Maglione D et al (1996) Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the placenta derived growth factor. Oncogene 13:577

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie, Universitätsklinikum Essen, Essen, Deutschland

    M. Becker, T. Szarvas & H. Rübben

  2. Institut für Anatomie, Universitätsklinikum Essen, 45122, Essen, Deutschland

    M. Becker &  S. Ergün

  3. Urologische Klinik und Poliklinik, Universitätsklinikum Großhadern, LMU, München, Deutschland

    D. Tilki

  4. Department of Genetic Medicine, Weill Cornell Medical College, New York, USA

    D. Tilki

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  1. M. Becker
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  5. S. Ergün
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Correspondence to S. Ergün.

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Becker, M., Tilki, D., Szarvas, T. et al. Urinbasierte Angiogenesemarker beim Urothelkarzinom der Harnblase. Urologe 48, 609–614 (2009). https://doi.org/10.1007/s00120-009-1989-1

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  • DOI: https://doi.org/10.1007/s00120-009-1989-1

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