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Tumor Biology

, Volume 35, Issue 6, pp 6089–6094 | Cite as

NRP-1 expression in bladder cancer and its implications for tumor progression

  • Wen Cheng
  • Dian Fu
  • Zhi-Feng Wei
  • Feng Xu
  • Xiao-Feng Xu
  • You-Huang Liu
  • Jing-Ping Ge
  • Feng Tian
  • Cong-Hui Han
  • Zheng-Yu Zhang
  • Li-Ming Zhou
Research Article

Abstract

Neuropilin-1 (NRP-1) overexpression has been reported in a variety of human cancers. However, the role of NRP-1 in bladder cancer (BC) remains unclear. The aim of present study was to analyze NRP-1 protein expression in BC tissues and to assess its prognostic significance for BC. NRP-1 messenger ribonucleic acid (mRNA) and protein expression were determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry in specimens of primary cancer and their adjacent noncancerous tissues in BC patients. Additionally, NRP-1 protein expression in 139 archived paraffin-embedded BC samples was analyzed by immunohistochemistry and correlated with clinicopathological characteristics and survival. Student’s t test, Spearman’s rank correlation, Kaplan-Meier plots, and Cox’s proportional hazards regression model were used to analyze the data. By qRT-PCR and immunohistochemistry, the levels of NRP-1 mRNA and protein were significantly higher in BC, compared to that in adjacent noncancerous tissues (P < 0.001). High expression of NRP-1 was significantly associated with histologic grade (P = 0.016) and tumor stage (P = 0.001). Multivariate analysis showed that high expression of NRP-1 was an independent prognostic factor for overall survival. Our study suggests that overexpression of NRP-1 may play an important role in the progression of BC, and NRP-1 expression may serve as a biomarker for poor prognosis for BC.

Keywords

Neuropilin-1 Bladder cancer Prognosis 

Notes

Acknowledgments

This work was also supported by the National Natural Science Foundation of China (No. 30772278 and No. 30973443).

Conflicts of interest

None.

References

  1. 1.
    Liou LS. Urothelial cancer biomarkers for detection and surveillance. Urology. 2006;67:25–33. doi: 10.1016/j.urology.2006.01.034. discussion 33–24.CrossRefPubMedGoogle Scholar
  2. 2.
    Smaldone MC, Jacobs BL, Smaldone AM, Hrebinko Jr RL. Long-term results of selective partial cystectomy for invasive urothelial bladder carcinoma. Urology. 2008;72:613–6. doi: 10.1016/j.urology.2008.04.052.CrossRefPubMedGoogle Scholar
  3. 3.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell. 1997;90:739–51.CrossRefPubMedGoogle Scholar
  4. 4.
    Kolodkin AL, Levengood DV, Rowe EG, Tai YT, Giger RJ, Ginty DD. Neuropilin is a semaphorin III receptor. Cell. 1997;90:753–62. doi: 10.1016/S0092-8674(00)80535-8.CrossRefPubMedGoogle Scholar
  5. 5.
    Kitsukawa T, Shimono A, Kawakami A, Kondoh H, Fujisawa H. Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development. 1995;121:4309–18.PubMedGoogle Scholar
  6. 6.
    Kawasaki T, Kitsukawa T, Bekku Y, Matsuda Y, Sanbo M, Yagi T, et al. A requirement for neuropilin-1 in embryonic vessel formation. Development. 1999;126:4895–902.PubMedGoogle Scholar
  7. 7.
    Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M. Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J. 2000;14:2532–9. doi: 10.1096/fj.00-0250com.CrossRefPubMedGoogle Scholar
  8. 8.
    Ding H, Wu X, Roncari L, Lau N, Shannon P, Nagy A, et al. Expression and regulation of neuropilin-1 in human astrocytomas. Int J Cancer. 2000;88:584–92.CrossRefPubMedGoogle Scholar
  9. 9.
    Latil A, Bièche I, Pesche S, Valéri A, Fournier G, Cussenot O, et al. VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms. Int J Cancer. 2000;89:167–71.CrossRefPubMedGoogle Scholar
  10. 10.
    Fakhari M, Pullirsch D, Abraham D, Paya K, Hofbauer R, Holzfeind P, et al. Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and −2 in human neuroblastoma. Cancer. 2002;94:258–63.CrossRefPubMedGoogle Scholar
  11. 11.
    Kawakami T, Tokunaga T, Hatanaka H, Kijima H, Yamazaki H, Abe Y, et al. Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer. 2002;95:2196–201. doi: 10.1002/cncr.10936.CrossRefPubMedGoogle Scholar
  12. 12.
    Akagi M, Kawaguchi M, Liu W, McCarty MF, Takeda A, Fan F, et al. Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells. Br J Cancer. 2003;88:796–802. doi: 10.1038/sj.bjc.6600811.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Parikh AA, Liu WB, Fan F, Stoeltzing O, Reinmuth N, Bruns CJ, et al. Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Cancer. 2003;98:720–9. doi: 10.1002/cncr.11560.CrossRefPubMedGoogle Scholar
  14. 14.
    Hansel DE, Wilentz RE, Yeo CJ, Schulick RD, Montgomery E, Maitra A. Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract. Am J Surg Pathol. 2004;28:347–56.CrossRefPubMedGoogle Scholar
  15. 15.
    Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, et al. Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res. 2001;61:5736–40.PubMedGoogle Scholar
  16. 16.
    Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M, Harriott P, et al. A peptide corresponding to the neuropilin-1-binding site on VEGF(165) induces apoptosis of neuropilin-1-expressing breast tumour cells. Br J Cancer. 2005;92:328–33. doi: 10.1038/sj.bjc.6602308.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Bachelder RE, Wendt MA, Mercurio AM. Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res. 2002;62:7203–6.PubMedGoogle Scholar
  18. 18.
    Bachelder RE, Lipscomb EA, Lin X, Wendt MA, Chadborn NH, Eickholt BJ, et al. Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Cancer Res. 2003;63:5230–3.PubMedGoogle Scholar
  19. 19.
    Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, et al. Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol. 2004;164:2139–51.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Tomizawa Y, Sekido Y, Kondo M, Gao B, Yokota J, Roche J, et al. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 Candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A. 2001;98:13954–9. doi: 10.1073/pnas.231490898.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Tse C, Xiang RH, Bracht T, Naylor SL. Human semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res. 2002;62:542–6.PubMedGoogle Scholar
  22. 22.
    Castro-Rivera E, Ran S, Thorpe P, Minna JD. Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci U S A. 2004;101:11432–7. doi: 10.1073/pnas.0403969101.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Gospodarowicz MK. Staging of bladder cancer. Semin Surg Oncol. 1994;10:51–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Hussain SA, James ND. Molecular markers in bladder cancer. Semin Radiat Oncol. 2005;15:3–9. doi: 10.1016/j.semradonc.2004.07.007.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Urology, Nanjing Jinling HospitalNanjing University School of MedicineNanjingChina
  2. 2.Department of Urology, The Affiliated School of Clinical Medicine of Xuzhou Medical CollegeXuzhou Central HospitalXuzhouChina

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