Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Basic Research

Relationship between the localization of fibroblast growth factor 9 in prostate cancer cells and postoperative recurrence

Prostate Cancer and Prostatic Diseases volume 15, pages 8–14 (2012)Cite this article

Abstract

Background:

Fibroblast growth factor 9 (FGF9) enhances cell proliferation and invasiveness in several malignant diseases. The aim of the present study is to investigate the role of FGF9 in postoperative recurrence after radical prostatectomy.

Methods:

Cell viability and invasion of LNCaP cells were assessed using MTT assay and Matrigel invasion assay, respectively, in the presence or absence of treatment with recombinant FGF9. Tissues obtained during a radical prostatectomy in 133 male patients were immunohistochemically stained using anti-FGF9 antibody.

Results:

Cell viability and invasion of LNCaP was significantly enhanced by treatment with recombinant FGF9. Immunohistochemical staining detected FGF9-positive cells in 20 samples. The prevalence of FGF9-positive cells in cases with a Gleason score of 8 or higher was 34.2%, which was significantly higher than that in those with Gleason scores of 7 or lower (7.3%, P=0.0003), respectively. The 3-year biochemical relapse-free survival rate was 17.5% in cases with FGF9-positive cells, which was significantly lower than that in cases in which FGF9-positive cells were not detectable (75.5%, P<0.0001).

Conclusions:

These results indicate that FGF9 can stimulate proliferation and invasion in prostate cancer cells, thus FGF9 could be a candidate of a predictive factor for recurrence after radical prostatectomy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Jin C, Wang F, Wu X, Yu C, Luo Y, McKeehan WL . Directionally specific paracrine communication mediated by epithelial FGF9 to stromal FGFR3 in two-compartment premalignant prostate tumors. Cancer Res 2007; 64: 4555–4562.

    Article  Google Scholar 

  2. Wu X, Jin C, Wang F, Yu C, McKeehan WL . Stromal cell heterogeneity in fibroblast growth factor-mediated stromal-epithelial cell cross-talk in premalignant prostate tumors. Cancer Res 2003; 63: 4936–4944.

    CAS  PubMed  Google Scholar 

  3. Giri D, Ropiquet F, Ittmann M . FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells. J Cell Physiol 1999; 180: 53–60.

    Article  CAS  PubMed  Google Scholar 

  4. Todo T, Kondo T, Kirino T, Asai A, Adams EF, Nakamura S et al. Expression and growth stimulatory effect of fibroblast growth factor 9 in human brain tumors. Neurosurgery 1998; 43: 337–346.

    Article  CAS  PubMed  Google Scholar 

  5. Hendrix ND, Wu R, Kuick R, Schwartz DR, Fearon ER, Cho KR . Ovarian ca wnt Fibroblast growth factor 9 has oncogenic activity and is a downstream target of Wnt signaling in ovarian endometrioid adenocarcinomas. Cancer Res 2006; 66: 1354–1362.

    Article  CAS  PubMed  Google Scholar 

  6. Wang CK, Chang H, Chen PH, Chang JT, Kuo YC, Ko JL et al. Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas. Int J Cancer 2009; 125: 807–815.

    Article  CAS  PubMed  Google Scholar 

  7. Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277–300.

    Article  PubMed  Google Scholar 

  8. Mori R, Dorff TB, Xiong S, Tarabolous CJ, Ye W, Groshen S et al. The relationship between proangiogenic gene expression levels in prostate cancer and their prognostic value for clinical outcomes. Prostate 2010; 70: 1692–1700.

    Article  CAS  PubMed  Google Scholar 

  9. Perez CA, Chen H, Shyr Y, Courtney R, Zheng W, Cai Q et al. The EGFR polymorphism rs884419 is associated with freedom from recurrence in patients with resected prostate cancer. J Urol 2010; 183: 2062–2069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xu B, Mi YY, Min ZC, Cheng G, Tong N, Tao J et al. p53 codon 72 increased biochemical recurrence risk after radical prostatectomy in a Southern Chinese population. Urol Int 2010; 85: 401–405.

    Article  CAS  PubMed  Google Scholar 

  11. Li ZG, Mathew P, Yang J, Starbuck MW, Zurita AJ, Liu J et al. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. J Clin Invest 2008; 118: 2697–2710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ueng TH, Chang YL, Tsai YY, Su JL, Chan PK, Shih JY et al. Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma. Arch Toxicol 2010; 84: 651–660.

    Article  CAS  PubMed  Google Scholar 

  13. Ohara S, Oue N, Matsubara A, Mita K, Hasegawa Y, Hayashi T et al. Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer. Cancer Sci 2008; 99: 1570–1577.

    Article  CAS  PubMed  Google Scholar 

  14. Yasui W, Ayhan A, Kitadai Y, Nishimura K, Yokozaki H, Ito H et al. Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas. Int J Cancer 1993; 53: 36–41.

    Article  CAS  PubMed  Google Scholar 

  15. Naruo K, Seko C, Kuroshima K, Matsutani E, Sasada R, Kondo T et al. Novel secretory heparin-binding factors from human glioma cells (glia-activating factors) involved in glial cell growth. Purification and biological properties. J Biol Chem 1993; 268: 2857–2864.

    CAS  PubMed  Google Scholar 

  16. Robinson D, Hasharoni A, Oganesian A, Sandell LJ, Yayon A, Nevo Z . Role of FGF9 and FGF receptor 3 in osteochondroma formation. Orthopedics 2001; 24: 783–787.

    CAS  PubMed  Google Scholar 

  17. Hiramatsu R, Harikae K, Tsunekawa N, Kurohmaru M, Matsuo I, Kanai Y . FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis differentiation. Development 2010; 137: 303–312.

    Article  CAS  PubMed  Google Scholar 

  18. Schmahl J, Kim Y, Colvin JS, Ornitz DM, Capel B . Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development 2004; 131: 3627–3636.

    Article  CAS  PubMed  Google Scholar 

  19. Behr B, Leucht P, Longaker MT, Quarto N . Fgf-9 is required for angiogenesis and osteogenesis in long bone repair. Proc Natl Acad Sci USA 2010; 107: 11853–11858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Klein RD, Maliner-Jongewaard MS, Udayakumar TS, Boyd JL, Nagle RB, Bowden GT . Promatrilysin expression is induced by fibroblast growth factors in the prostatic carcinoma cell line LNCaP but not in normal primary prostate epithelial cells. Prostate 1999; 41: 215–223.

    Article  CAS  PubMed  Google Scholar 

  21. Miyagi N, Kato S, Terasaki M, Shigemori M, Morimatsu M . Fibroblast growth factor-2 and -9 regulate proliferation and production of matrix metalloproteinases in human gliomas. Int J Oncol 1998; 12: 1085–1090.

    CAS  PubMed  Google Scholar 

  22. Trock BJ, Guo CC, Gonzalgo ML, Magheli A, Loeb S, Epstein JI . Tertiary Gleason patterns and biochemical recurrence after prostatectomy: proposal for a modified Gleason scoring system. J Urol 2009; 182: 1364–1370.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hattab EM, Koch MO, Eble JN, Lin H, Cheng L . Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma. J Urol 2006; 175: 1695–1699.

    Article  PubMed  Google Scholar 

  24. Harada M, Murakami H, Okawa A, Okimoto N, Hiraoka S, Nakahara T et al. FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion. Nat Genet 2009; 41: 289–298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was carried out at the Analysis Center of Life Science, Hiroshima University.

Author information

Authors and Affiliations

  1. Department of Urology, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    J Teishima, K Shoji, T Hayashi, K Miyamoto, S Ohara & A Matsubara

Authors
  1. J Teishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Shoji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Matsubara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Teishima.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teishima, J., Shoji, K., Hayashi, T. et al. Relationship between the localization of fibroblast growth factor 9 in prostate cancer cells and postoperative recurrence. Prostate Cancer Prostatic Dis 15, 8–14 (2012). https://doi.org/10.1038/pcan.2011.48

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2011.48

Keywords

This article is cited by

Search

Advanced search

Quick links