Skip to main content

Advertisement

SpringerLink
Log in

MMP-9 expression in meningiomas: a prognostic marker for recurrence risk?

  • Lab Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Despite total macroscopic resection of meningiomas relapses do occur in these tumours, possibly because of microscopic clusters of neoplastic cells left in the dura mater or in the arachnoid membrane. The invasiveness of the neoplastic cells of human meningiomas has been related to expression of matrix-metalloproteinase-9 (MMP-9), a peptidase actively implicated in the degradation of the extracellular matrix; nonetheless, the prognostic value of MMP-9 in the risk of recurrence of meningiomas has not been sufficiently investigated. Herein, we analysed MMP-9 expression in a series of meningiomas of different histotype and histological grade and assessed its correlation with various clinico-pathological indicators and with the clinical outcome of these tumours. We also tested the eventual pro-angiogenic role of MMP-9 expression in meningiomas through its correlation with vascular endothelial growth factor (VEGF) and microvessel density (MVD) revealed in the same cases. MMP-9 expression was observed in 64% of cases; high expression of this protein was significantly associated with high histological grade and proliferation index, but not with high MVD, of the tumours. A trend towards correlation between MMP-9 and VEGF expression was found, although statistical significance was not reached. In addition, high MMP-9 expression was a negative independent prognostic factor associated with higher recurrence risk in totally resected meningiomas. In conclusion, we demonstrated for the first time the potential prognostic value of MMP-9 expression in meningiomas. Inhibition of MMP-9 may be a new therapeutic strategy to prevent recurrences of meningiomas, particularly the high-grade type.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Perry A, Stafford SL, Scheithauer BW, Lohse CM, Wollan PC (1999) “Malignancy” in meningiomas: a clinico-pathological study of 116 patients with grading implications. Cancer 85:2046–2056

    PubMed  CAS  Google Scholar 

  2. Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39

    Article  PubMed  CAS  Google Scholar 

  3. Kamitani H, Masuzawa H, Kanazawa I, Kubo T (2001) Recurrence of convexity meningiomas: tumour cells in the arachnoid membrane. Surg Neurol 56:228–235

    Article  PubMed  CAS  Google Scholar 

  4. Kinjo T, al-Mefty O, Kanaan I (1993) Grade zero removal of supratentorial convexity meningiomas. Neurosurgery 33:394–399

    Article  PubMed  CAS  Google Scholar 

  5. Chang C, Werb Z (2001) The many faces of metalloproteinases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol 11:S37–S43

    PubMed  CAS  Google Scholar 

  6. Mizoue T, Kawamoto H, Arita K, Tominaga A, Kurisu K (1999) Secretion of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by meningiomas detected by cell immunoblot analysis. Acta Neurochir 141:481–486

    Article  CAS  Google Scholar 

  7. Nordqvist AC, Smurawa H, Mathiesen T (2001) Expression of matrix metalloproteinases 2 and 9 in meningiomas associated with different degrees of brain invasiveness and edema. J Neurosurg 95:839–844

    Article  PubMed  CAS  Google Scholar 

  8. Paek SH, Kim CY, Kim YY, Park IA, Kim MS, Kim DG, Jung HW (2002) Correlation of clinical and biological parameters with peritumoral edema in meningioma. J Neurooncol 60:235–245

    Article  PubMed  Google Scholar 

  9. Rooprai HK, van Meter TE, Robinson SD, King A, Rucklidge GJ, Pilkington GJ (2003) Expression of MMP-2 and -9 in short-term cultures of meningioma: influence of histological subtype. Int J Mol Med 12:977–981

    PubMed  CAS  Google Scholar 

  10. Okada M, Miyake K, Matsumoto Y, Kawai N, Kunishio K, Nagao S (2004) Matrix metalloproteinase-2 and matrix metalloproteinase-9 expressions correlate with the recurrence of intracranial meningiomas. J Neurooncol 66:29–37

    Article  PubMed  Google Scholar 

  11. von Randow AJ, Schindler S, Tews DS (2006) Expression of extracellular matrix-degrading proteins in classic, atypical, and anaplastic meningiomas. Pathol Res Pract 202:365–372

    Article  Google Scholar 

  12. Panagopoulos AT, Lancellotti CL, Veiga JC, de Aguiar PH, Colquhoun A (2008) Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas. J Neurooncol 89:73–87

    Article  PubMed  Google Scholar 

  13. Bellon G, Caulet T, Cam Y, Pluot M, Poulin M, Pytlinska M, Bernard MH (1985) Immunohistochemical localisation of macromolecules of the basement membrane and extracellular matrix of human gliomas and meningiomas. Acta Neuropathol 66:245–252

    Article  PubMed  CAS  Google Scholar 

  14. Ng HK, Wong AT (1993) Expression of epithelial and extracellular matrix protein markers in meningiomas. Histopathology 22:113–125

    Article  PubMed  CAS  Google Scholar 

  15. Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270

    Article  PubMed  CAS  Google Scholar 

  16. 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 

  17. Ebrahem Q, Chaurasia SS, Vasanji A, Qi JH, Klenotic PA, Cutler A, Asosingh K, Erzurum S, Anand-Apte B (2010) Cross-talk between vascular endothelial growth factor and matrix metalloproteinases in the induction of neovascularization in vivo. Am J Pathol 176:496–503

    Article  PubMed  CAS  Google Scholar 

  18. Perry A, Louis DN, Scheithauer BW (2007) Meningiomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK et al (eds) WHO Classification of Tumors of the Central Nervous System. IARCC press, Lyon, pp 164–172

    Google Scholar 

  19. Barresi V, Cerasoli S, Vitarelli E, Tuccari G (2007) Density of microvessel positive for CD105 (endoglin) is related to prognosis in meningiomas. Acta Neuropathol 114:147–156

    Article  PubMed  CAS  Google Scholar 

  20. Barresi V, Cerasoli S, Tuccari G (2008) Correlative evidence that tumor cell-derived caveolin-1 mediates angiogenesis in meningiomas. Neuropathology 28:472–478

    Article  PubMed  Google Scholar 

  21. Barresi V, Vitarelli E, Cerasoli S (2009) Semaphorin3A immunohistochemical expression in human meningiomas: correlation with the microvessel density. Virchows Arch 454:563–571

    Article  PubMed  CAS  Google Scholar 

  22. Barresi V, Tuccari G (2010) Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human meningiomas. Neuropathology. doi:10.1111/j.1440-1789.2010.01105.x

  23. Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM (1998) The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas. Cancer 82:2262–2269

    Article  PubMed  CAS  Google Scholar 

  24. Ennis BW, Matrisian LM (1994) Matrix degrading metalloproteinases. J Neurooncol 18:105–109

    Article  PubMed  CAS  Google Scholar 

  25. Jaaskelainen J (1986) Seemingly complete removal of histologically benign intracranial meningioma: late recurrence rate and factors predicting recurrence in 657 patients. A multivariate analysis. Surg Neurol 26:461–469

    Article  PubMed  CAS  Google Scholar 

  26. Tummalapalli P, Spomar D, Gondi CS, Olivero WC, Gujrati M, Dinh DH, Rao JS (2007) RNAi-mediated abrogation of cathepsin B and MMP-9 gene expression in a malignant meningioma cell line leads to decreased tumor growth, invasion and angiogenesis. Int J Oncol 31:1039–1050

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  28. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25

    Article  PubMed  CAS  Google Scholar 

  29. Christov C, Lechapt-Zalcman E, Adle-Biassette H, Nachev S, Gherardi RK (1999) Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptor flt-1 in microcystic meningiomas. Acta Neuropathol 98:414–420

    Article  PubMed  CAS  Google Scholar 

  30. Zhang X, Yamashita M, Uetsuki H, Kakehi Y (2002) Angiogenesis in renal cell carcinoma: evaluation of microvessel density, vascular endothelial growth factor and matrix metalloproteinases. Int J Urol 9:509–514

    Article  PubMed  CAS  Google Scholar 

  31. Das A, Tan WL, Smith D (2003) Expression of extracellular matrix markers in benign meningiomas. Neuropathology 23:275–281

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Pathology, University of Messina, Messina, Italy

    V. Barresi, E. Vitarelli, G. Tuccari & G. Barresi

  2. Dipartimento di Patologia Umana, Policlinico Universitario G. Martino, Pad D, Via Consolare Valeria, 98125, Messina, Italy

    V. Barresi

Authors
  1. V. Barresi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Vitarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Tuccari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Barresi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Barresi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barresi, V., Vitarelli, E., Tuccari, G. et al. MMP-9 expression in meningiomas: a prognostic marker for recurrence risk?. J Neurooncol 102, 189–196 (2011). https://doi.org/10.1007/s11060-010-0312-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-010-0312-8

Keywords

Search

Navigation