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Collagenase-3 expression by tumor cells and gelatinase B expression by stromal fibroblast-like cells are associated with biochemical recurrence after radical prostatectomy in patients with prostate cancer

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Abstract

Purpose

To investigate the possible clinical value of the expression of MMPs and their tissue inhibitors (TIMPs) by the different cellular types of the tumor scenario to predict biochemical recurrence in patients undergoing radical prostatectomy due clinically localized prostate cancer.

Methods

An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13 and 14 and TIMPs-1, 2 and 3 on cancer specimens from 133 patients with clinical localized prostate carcinoma.

Results

Immunostaining for all the proteins studied was localized predominantly in tumor cells, but also in stromal cells in a significant percentage of prostate carcinomas, ranged from 20 to 50% for several proteins in fibroblast-like cells and in mononuclear inflammatory cells. Multivariate analysis according to a Cox model demonstrated that tumor stage (P < 0.0001) and Gleason grading (grades 7–10: 2.08 (1.1–3.9); P < 0.05) were significantly and independently associated with biochemical recurrence. Additionally, the expression of MMP-9 by fibroblast-like cells (P < 0.01) and MMP-13 by tumor cells (P < 0.05) were also variables significantly and independently associated with biochemical recurrence.

Conclusions

MMP-13 expression by tumor cells and MMP-9 by stromal fibroblast-like cells were independent factors of biochemical recurrence in prostate cancer.

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References

  1. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174

    Article  PubMed  CAS  Google Scholar 

  2. Noel A, Boulay A, Kebers F, Kannan R, Hajitou A, Calberg-Bacq CM, Basset P, Rio MC, Foidart JM (2000) Demonstration in vivo that stromelysin-3 functions through its proteolytic activity. Oncogene 19:1605–1612

    Article  PubMed  CAS  Google Scholar 

  3. Stetler-Stevenson WG (1999) Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 103:1237–1241

    Article  PubMed  CAS  Google Scholar 

  4. Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM (2001) Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia 3:459–468

    Article  PubMed  CAS  Google Scholar 

  5. Jiang Y, Goldberg ID, Shi YE (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21:2245–2252

    Article  PubMed  CAS  Google Scholar 

  6. Wurtz SO, Schrohl AS, Sorensen NM, Lademann U, Christensen IJ, Mouridsen H, Brunner N (2005) Tissue inhibitor of metalloproteinases-1 in breast cancer. Endocr Relat Cancer 12:215–227

    Article  PubMed  CAS  Google Scholar 

  7. Zhang SX, Bentel JM, Ricciardelli C, Horsfall DJ, Haagensen DE, Marshall VR, Tilley WD (1998) Immunolocalization of apolipoprotein D, androgen receptor and prostate specific antigen in early stage prostate cancers. J Urol 159:548–554

    Article  PubMed  CAS  Google Scholar 

  8. Riddick AC, Shukla CJ, Pennington CJ, Bass R, Nuttall RK, Hogan A, Sethia KK, Ellis V, Collins AT, Maitland NJ et al (2005) Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 92:2171–2180

    Article  PubMed  CAS  Google Scholar 

  9. Morgia G, Falsaperla M, Malaponte G, Madonia M, Indelicato M, Travali S, Mazzarino MC (2005) Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urol Res 33:44–50

    Article  PubMed  CAS  Google Scholar 

  10. Semaan M, Jovenin N, Birembaut P, Menard J, Staerman F (2005) Prognostic value of stromal immunolabelling by MMP-2, MT1-MMP and TIMP-2 in clinically localized prostate cancer. Prog Urol 15:250–254

    PubMed  Google Scholar 

  11. Parker RL, Huntsman DG, Lesack DW, Cupples JB, Grant DR, Akbari M, Gilks CB (2002) Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 117:723–728

    Article  PubMed  Google Scholar 

  12. Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868

    Article  PubMed  CAS  Google Scholar 

  13. Gonzalez LO, Pidal I, Junquera S, Corte MD, Vazquez J, Rodriguez JC, Lamelas ML, Merino AM, Garcia-Muniz JL, Vizoso FJ (2007) Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse. Br J Cancer 97:957–963

    Article  PubMed  CAS  Google Scholar 

  14. Del Casar JM, Gonzalez LO, Alvarez E, Junquera S, Marin L, Gonzalez L, Bongera M, Vazquez J, Vizoso FJ (2009) Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas. Breast Cancer Res Treat

  15. Varani J, Hattori Y, Dame MK, Schmidt T, Murphy HS, Johnson KJ, Wojno KJ (2001) Matrix metalloproteinases (MMPs) in fresh human prostate tumour tissue and organ-cultured prostate tissue: levels of collagenolytic and gelatinolytic MMPs are low, variable and different in fresh tissue versus organ-cultured tissue. Br J Cancer 84:1076–1083

    Article  PubMed  CAS  Google Scholar 

  16. Liotta LA, Kohn EC (2001) The microenvironment of the tumour-host interface. Nature 411:375–379

    Article  PubMed  CAS  Google Scholar 

  17. Chantrain CF, Shimada H, Jodele S, Groshen S, Ye W, Shalinsky DR, Werb Z, Coussens LM, DeClerck YA (2004) Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment. Cancer Res 64:1675–1686

    Article  PubMed  CAS  Google Scholar 

  18. Pellikainen JM, Ropponen KM, Kataja VV, Kellokoski JK, Eskelinen MJ, Kosma VM (2004) Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clin Cancer Res 10:7621–7628

    Article  PubMed  CAS  Google Scholar 

  19. Chung LW, Chang SM, Bell C, Zhau HE, Ro JY, von Eschenbach AC (1989) Co-inoculation of tumorigenic rat prostate mesenchymal cells with non-tumorigenic epithelial cells results in the development of carcinosarcoma in syngeneic and athymic animals. Int J Cancer 43:1179–1187

    Article  PubMed  CAS  Google Scholar 

  20. Hayward SW, Wang Y, Cao M, Hom YK, Zhang B, Grossfeld GD, Sudilovsky D, Cunha GR (2001) Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Cancer Res 61:8135–8142

    PubMed  CAS  Google Scholar 

  21. Dong Z, Kumar R, Yang X, Fidler IJ (1997) Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 88:801–810

    Article  PubMed  CAS  Google Scholar 

  22. Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD (1998) Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol 161:6845–6852

    PubMed  CAS  Google Scholar 

  23. Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaisse J (2000) Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett 486:247–251

    Article  PubMed  CAS  Google Scholar 

  24. Tu G, Xu W, Huang H, Li S (2008) Progress in the development of matrix metalloproteinase inhibitors. Curr Med Chem 15:1388–1395

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by GLAXOSMITHKLINE, S.A.

Conflict of interest

The authors indicated no potential conflicts of interest.

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Correspondence to Francisco J. Vizoso.

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Escaff, S., Fernández, J.M., González, L.O. et al. Collagenase-3 expression by tumor cells and gelatinase B expression by stromal fibroblast-like cells are associated with biochemical recurrence after radical prostatectomy in patients with prostate cancer. World J Urol 29, 657–663 (2011). https://doi.org/10.1007/s00345-010-0595-6

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  • DOI: https://doi.org/10.1007/s00345-010-0595-6

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