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Published in: International Urology and Nephrology 2/2011

01-06-2011 | Urology - Original Paper

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

Authors: Chen-chen Feng, Qiang Ding, Yuan-fang Zhang, Hao-wen Jiang, Hui Wen, Pao-hsun Wang, Zhong Wu

Published in: International Urology and Nephrology | Issue 2/2011

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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.
Literature
1.
2.
go back to reference 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 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.
go back to reference 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 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
4.
go back to reference Forkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186CrossRef Forkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186CrossRef
5.
go back to reference Tombran-Tink J, Johnson LV (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700–1707PubMed Tombran-Tink J, Johnson LV (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700–1707PubMed
6.
go back to reference 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 43:821–829PubMed 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 43:821–829PubMed
7.
go back to reference 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 11:8737–8744PubMedCrossRef 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 11:8737–8744PubMedCrossRef
8.
go back to reference 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 17:937–944PubMed 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 17:937–944PubMed
9.
go back to reference 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 11:325–332PubMedCrossRef 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 11:325–332PubMedCrossRef
10.
go back to reference 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 6:419–425PubMedCrossRef 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 6:419–425PubMedCrossRef
11.
go back to reference 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 81:1256–1263PubMedCrossRef 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 81:1256–1263PubMedCrossRef
12.
go back to reference 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 40:236–243CrossRef 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 40:236–243CrossRef
13.
go back to reference 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 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
14.
go back to reference Rosai EJ (2004) Rosai and Ackerman’s surgical pathology, vol 1, 9th edn. Elsevier, China, pp 1317–1359 Rosai EJ (2004) Rosai and Ackerman’s surgical pathology, vol 1, 9th edn. Elsevier, China, pp 1317–1359
15.
go back to reference 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 6:140–147PubMedCrossRef 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 6:140–147PubMedCrossRef
16.
go back to reference Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934PubMed Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934PubMed
17.
go back to reference 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 87:1603–1612PubMedCrossRef 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 87:1603–1612PubMedCrossRef
18.
go back to reference Jeremy PC, Timothy SO, Adrian LH (1996) Bladder cancer angiogenesis, its role in recurrence, stage progression and as a therapeutic target. Cancer Metastasis Rev 15:221–230CrossRef Jeremy PC, Timothy SO, Adrian LH (1996) Bladder cancer angiogenesis, its role in recurrence, stage progression and as a therapeutic target. Cancer Metastasis Rev 15:221–230CrossRef
19.
go back to reference 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 2:737–744PubMedCrossRef 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 2:737–744PubMedCrossRef
20.
go back to reference Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 146:1029–1039PubMed Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 146:1029–1039PubMed
21.
go back to reference 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 98:12485–12490PubMedCrossRef 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 98:12485–12490PubMedCrossRef
22.
go back to reference 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 205:854–857CrossRef 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 205:854–857CrossRef
23.
go back to reference Ren JG, Jie C, Talbot C (2005) How PEDF prevents angiogenesis: a hypothesized pathway. Med Hypotheses 64:74–78PubMedCrossRef Ren JG, Jie C, Talbot C (2005) How PEDF prevents angiogenesis: a hypothesized pathway. Med Hypotheses 64:74–78PubMedCrossRef
24.
go back to reference 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 4:1317–1326PubMed 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 4:1317–1326PubMed
25.
go back to reference Liotta LA (1986) Tumor invasion and metastasis-role of extracellular matrix: Rhoada Memorial Award lecture. Cancer Res 46:1PubMedCrossRef Liotta LA (1986) Tumor invasion and metastasis-role of extracellular matrix: Rhoada Memorial Award lecture. Cancer Res 46:1PubMedCrossRef
26.
go back to reference 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 91:99PubMedCrossRef 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 91:99PubMedCrossRef
27.
go back to reference 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 9:2576–2582PubMed 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 9:2576–2582PubMed
Metadata
Title
Pigment epithelium-derived factor expression is down-regulated in bladder tumors and correlates with vascular endothelial growth factor and matrix metalloproteinase-9
Authors
Chen-chen Feng
Qiang Ding
Yuan-fang Zhang
Hao-wen Jiang
Hui Wen
Pao-hsun Wang
Zhong Wu
Publication date
01-06-2011
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 2/2011
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-010-9834-4

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