Skip to main content

Advertisement

SpringerLink
Log in

Pigment epithelium-derived factor expression is down-regulated in bladder tumors and correlates with vascular endothelial growth factor and matrix metalloproteinase-9

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Growth of solid tumor depends on angiogenesis, a process regulated by the balance of pro- and anti-angiogenic factors. We investigated the expression of anti-angiogenic factor pigment epithelium-derived factor (PEDF) and proangiogenic factors vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) with immunohistochemistry in 64 bladder tumor samples and 23 normal controls. Compared with normal urothelium, we identified decreased PEDF expression (P = 0.000) whereas increased expression of VEGF (P = 0.000) and MMP-9 (P = 0.000) in tumorous tissue as well as in papillary urothelial neoplasm of low malignant potential (PUNLMP) (P = 0.009 and P = 0.000 accordingly) but MMP-9 (P = 0.704). Decreased PEDF expression was revealed with higher tumor grade (P = 0.014) but stage (P = 0.687). There was no age or gender preference in PEDF, VEGF or MMP-9 expression. Negative correlation of expression in tumorous and cancerous tissue regarding PEDF and VEGF (P = 0.000, r = −0.56, and P = 0.000, r = −0.50, respectively), PEDF and MMP-9 (P = 0.002, r = −0.39, and P = 0.032, r = −0.30, respectively) was identified. There was a negative correlation of expression between PEDF and VEGF (P = 0.016, r = −0.677) and no correlation between PEDF and MMP-9 (P = 0.147, r = −0.45) in PUNLMP. Decreased PEDF and increased VEGF and MMP-9 expression may play considerable roles in differentiation and invasion of bladder tumor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3:401–410

    Article  PubMed  CAS  Google Scholar 

  2. Ferley J, Bray F, Pisani P, Parkin DM (2001) Globalcan 2000: cancer incidence, mortality and prevalence worldwide, version 1.0 LARC Cancer Base No.5, IARC Press, Lyon

  3. Babjuk M, Oosterlinck W, Sylvester R, Kassinen E, Böhle A, Palou J (2008) Guidelines on TaT1 (non-muscle invasive) bladder cancer. European Association of Urology Guidelines. European Association of Urology, Arnhem, The Netherlands, pp 3–21

    Google Scholar 

  4. Forkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  Google Scholar 

  5. Tombran-Tink J, Johnson LV (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700–1707

    PubMed  CAS  Google Scholar 

  6. Duh EJ, Yang HS, Suzuma I, Miyagi M, Youngman E, Mori K, Katai M, Yan L, Suzuma K, West K, Davarya S, Tong P, Gehlbach P, Pearlman J, Crabb JW, Aiello LP, Campochiaro PA, Zack DJ (2002) Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci 43:821–829

    PubMed  Google Scholar 

  7. Hase R, Miyamoto M, Uehara H, Kadoya M, Ebihara Y, Murakami Y, Takahashi R, Mega S, Li L, Shichinohe T, Kawarada Y, Kondo S (2005) Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice. Clin Cancer Res 11:8737–8744

    Article  PubMed  CAS  Google Scholar 

  8. Zhang LJ, Chen JF, Ke Y, Mansel RE, Jiang WG (2006) Expression of pigment epithelium derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome. Int J Mol Med 17:937–944

    PubMed  CAS  Google Scholar 

  9. Guan M, Pang CP, Yam HF, Cheung KF, Liu WW, Lu Y (2004) Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor. Cancer Gene Ther 11:325–332

    Article  PubMed  CAS  Google Scholar 

  10. Guan M, Jiang H, Xu C, Xu R, Chen Z, Lu Y (2007) Adenovirus-mediated PEDF expression inhibits prostate cancer cell growth and results in augmented expression of PAI-2. Cancer Biol Ther 6:419–425

    Article  PubMed  CAS  Google Scholar 

  11. Zhang T, Guan M, Xu C, Chen YM, Lu Y (2007) Pigment epithelium-derived factor inhibits glioma cell growth in vitro and in vivo. Life Sci 81:1256–1263

    Article  PubMed  CAS  Google Scholar 

  12. Christian JS, Zhang YB, Zhou JF, Ng C, Nathwani AC, Davidoff AM (2005) Adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth. J Pediatr Surg 40:236–243

    Article  Google Scholar 

  13. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) (2004) World health organization classification of tumours, pathology and genetics of tumours of the urinary system and male genital organs. IARC Press, Lyon, pp 90–109

    Google Scholar 

  14. Rosai EJ (2004) Rosai and Ackerman’s surgical pathology, vol 1, 9th edn. Elsevier, China, pp 1317–1359

    Google Scholar 

  15. Ioachim E, Michael MC, Salmas M, Damala K, Tsanou E, Michael MM, Malamou-Mitsi V, Stavropoulos NE (2006) Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer 6:140–147

    Article  PubMed  CAS  Google Scholar 

  16. Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934

    PubMed  CAS  Google Scholar 

  17. Bochner BH, Cote RJ, Weidner N, Groshen S, Chen S, Skinner DG, Nichols PW (1995) Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst 87:1603–1612

    Article  PubMed  CAS  Google Scholar 

  18. Jeremy PC, Timothy SO, Adrian LH (1996) Bladder cancer angiogenesis, its role in recurrence, stage progression and as a therapeutic target. Cancer Metastasis Rev 15:221–230

    Article  Google Scholar 

  19. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744

    Article  PubMed  CAS  Google Scholar 

  20. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 146:1029–1039

    PubMed  CAS  Google Scholar 

  21. Rodríguez-Manzaneque JC, Lane TF, Ortega MA, Hynes RO, Lawler J, Iruela-Arispe ML (2001) Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc Natl Acad Sci U S A 98:12485–12490

    Article  PubMed  Google Scholar 

  22. Gamze D, Yurdaur S, Sancar B, Levent Y, Oguz A, Filiz K, Bedri K (2009) Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas. Pathol Res Pract 205:854–857

    Article  Google Scholar 

  23. Ren JG, Jie C, Talbot C (2005) How PEDF prevents angiogenesis: a hypothesized pathway. Med Hypotheses 64:74–78

    Article  PubMed  CAS  Google Scholar 

  24. Park JE, Keller GA, Ferrara N (1993) The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4:1317–1326

    PubMed  CAS  Google Scholar 

  25. Liotta LA (1986) Tumor invasion and metastasis-role of extracellular matrix: Rhoada Memorial Award lecture. Cancer Res 46:1

    Article  PubMed  CAS  Google Scholar 

  26. Nutt JE, Durkan GC, Mellon JK, Lunec J (2003) Matrix metalloproteinase (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine. BJU Int 91:99

    Article  PubMed  CAS  Google Scholar 

  27. Durkan GC, Nutt JE, Marsh C (2003) Alteration in urinary matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio predicts recurrence in nonmuscle-invasive bladder cancer. Clin Cancer Res 9:2576–2582

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We hereby owe our thanks to Dr ZHOU Zhong-wen and Mr ZHU Teng-fang for excellent technical support. This work was supported in part by Science and Technology Commission of Shanghai Municipality, China (No. 07ZR14018).

Author information

Authors and Affiliations

  1. Department of Urology, Huashan Hospital, Fudan University, 12 Central Urumqi Rd, Shanghai, 200040, People’s Republic of China

    Chen-chen Feng, Qiang Ding, Hao-wen Jiang, Hui Wen & Zhong Wu

  2. Institute of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China

    Yuan-fang Zhang

  3. Department of Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China

    Pao-hsun Wang

Authors
  1. Chen-chen Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan-fang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hao-wen Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pao-hsun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhong Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, Cc., Ding, Q., Zhang, Yf. et al. Pigment epithelium-derived factor expression is down-regulated in bladder tumors and correlates with vascular endothelial growth factor and matrix metalloproteinase-9. Int Urol Nephrol 43, 383–390 (2011). https://doi.org/10.1007/s11255-010-9834-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-010-9834-4

Keywords

Search

Navigation