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Signals of Apoptotic Pathways in Several Types of Meningioma

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Pathology & Oncology Research

Abstract

Meningiomas are intracranial tumour derived from meningothelial cells, which aggressive behaviour has been frequently associated to cell apoptosis. In this paper activation of several factors involved in apoptosis has been investigated on biopsies of primary, non recurrent meningiomas. Benign (meningotheliomatous, transitional, fibrous, angiomatous), atypical and anaplastic meningiomas were analysed by immunohistochemistry and western blot, to visualize the occurring of different apoptotic pathways and their association with clinical grading. Apoptotic cell have been detected by a double colorimetric staining for TUNEL and caspase-3 active form. Apoptotic signal positive cells have been detected in all type of meningiomas analysed, with exception of meningotheliomatous meningiomas. Differences have been found in the activation of apoptotic pathways between several types of grade I meningiomas and among benign, anaplastic and atypical meningiomas. An intense expression of several apoptotic inhibitor occurred in grade I meningiomas. The correlation among expression of apoptotic and inhibitory factors and cell proliferation index may suggest that in grade I meningiomas apoptosis may be related to mechanisms involved into tumor cells surviving. Instead in grade II and III meningiomas the same correlation seems indicate an high turnover of tumor cells that might be useful as index of cell proliferation and tumor mass growth.

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Abbreviations

c-Flip:

FLICE inhibitory protein

FLICE:

FADD-like IL-1β-converting enzyme

SDS:

Sodium Dodecyl Sulphate

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

XIAP:

X-linked inhibitor apoptotic protein

References

  1. Perry A, Stafford SL, Scheithauer BW et al (1997) Meningioma grading. An analysis of histologic parameters. Am J Surg Pathol 21:1455–1465

    Article  PubMed  CAS  Google Scholar 

  2. Perry A, Louis DN, Scheithauer BW et al (2007) World Health Organization classification of tumours of the central nervous system, 4th edn. IARC, Lyon, pp 164–172

    Google Scholar 

  3. Lowe SW, Jacks T, Housman DE et al (1994) Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc Natl Acad Sci USA 91:2026–2030

    Article  PubMed  CAS  Google Scholar 

  4. Hopkins-Donaldson S, Bodmer J, Balmas Bourloud K et al (2000) Loss of caspase-8 expression in highly malignant human neuroblastoma cells correlates with resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Cancer Res 60:4315–4319

    PubMed  CAS  Google Scholar 

  5. Kayaselcuk F, Zorludemir S, Bal N et al (2004) The expression of survivin and Ki-67 in meningiomas: correlation with grade and clinical outcome. J Neurooncol 67:209–214

    Article  PubMed  Google Scholar 

  6. Kostantinidou AE, Givalos N, Gakiopoulou H et al (2007) Caspase-3 immunohistochemical expression is a maker of apoposis, increased grade and early recurrence in intracranial meningiomas. Apoptosis 12:695–705

    Article  Google Scholar 

  7. Patel T, Gores GJ, Kaufmann SH (1996) The role of proteases during apoptosis. FASEB J 10:587–597

    PubMed  CAS  Google Scholar 

  8. Vermeulen K, Van Bockstaele DR, Berneman ZN (2005) Apoptosis: mechanisms and relevance in cancer. Ann Hematol 84:627–639

    Article  PubMed  CAS  Google Scholar 

  9. Elkon KB (1999) Caspases: multifunctional proteases. J Exp Med 12:1725–1727

    Article  Google Scholar 

  10. Schwerk C, Schulze-Osthoff K (2003) Non-apoptotic functions of caspases in cellular proliferation and differentiation. Biochem Pharmacol 66:1453–1458

    Article  PubMed  CAS  Google Scholar 

  11. Sasaki T, Lopes MB, Hankins GR, Helm GA (2002) Expression of surviving, an inhibitor of apoptosis protein, in tumors of the nervous system. Acta Neuropathol 104:105–109

    Article  PubMed  CAS  Google Scholar 

  12. Kim R, Emi R, Tanabe K, Murakami S, Uchida Y, Arihiro K (2006) Regulation and interplay of apoptotic and non-appoptotic cell death. J Pathol 208:319–326

    Article  PubMed  CAS  Google Scholar 

  13. Strasser A, O’Connor L, Dixit VM (2000) Apoptosis signalling. Annu Rev Biochem 69:217–245

    Article  PubMed  CAS  Google Scholar 

  14. Cowling V, Downward J (2002) Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain. Cell Death Diff 9:1046–1056

    Article  CAS  Google Scholar 

  15. Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326

    Article  PubMed  CAS  Google Scholar 

  16. Shimizu S, Narita M, Tsujimoto Y (1999) Bcl-2 family proteins regulate the release of apoptogenic cytochrome-c by the mitochrondial channel VDAC. Nature 399:483–487

    Article  PubMed  CAS  Google Scholar 

  17. Tang D, Kidd VJ (1998) Cleavage of DFF-45/ICAD by multiple caspases is essential for function during apoptosis. J Biol Chem 273:28549–28552

    Article  PubMed  CAS  Google Scholar 

  18. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS (2005) XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24:645–655

    Article  PubMed  CAS  Google Scholar 

  19. Matsumori Y, Northington FJ, Hong SM (2006) Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70. Stroke 37:507–512

    Article  PubMed  CAS  Google Scholar 

  20. Kostantinidou AE, Pavlopoulos PM, Patsouris E, Kaklamani L, Davaris P (1998) Expression of apoptotic and proliferation markers in meningiomas. J Pathol 186:325–330

    Article  Google Scholar 

  21. Charriaut-Marianque C, Ben Ari Y (1995) A cautionary note on the use of TUNEL stain to determine apoptosis. Neuroreport 7:61–64

    Google Scholar 

  22. Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schultze-Hermann R (1995) In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary role. Hepathology 21:1465–1468

    CAS  Google Scholar 

  23. Moreno RD, Lizama C, Urzua N, Vergara SP, Reyes JG (2006) Caspase activation throughout the first wave of spermatogenesis in the rat. Cell Tissue Res 325:533–540

    Article  PubMed  CAS  Google Scholar 

  24. Mosnier JF, Perret AG, Brunon J, Boucheron S (1996) Expression of the bcl-2 oncoprotein in meningiomas. Am J Pathol 106:652–659

    CAS  Google Scholar 

  25. Smith DW, Day TA (1993) Neurochemical identification of fos-positive neurons using two-colour immunoperoxidase staining. J Neurosci Methods 47:73–83

    Article  PubMed  CAS  Google Scholar 

  26. Renò F, Sabbatini M, Lombardi F, Stella M, Pezzato C, Magliacani G, Cannas M (2003) In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars. Wound Rep and Reg 11:331–336

    Article  Google Scholar 

  27. Das A, Tan W-L, Smith DR (2003) Expression of the inhibitor of apoptosis protein survivin in benign meningiomas. Cancer Lett 193:217–223

    Article  PubMed  CAS  Google Scholar 

  28. Jacobs TW, Prioleau JE, Stilman IE, Schnitt SJ (1996) Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Nat Cancer Inst 88:1054–1059

    Article  PubMed  CAS  Google Scholar 

  29. Takei H, Buckleair W, Powell SZ (2008) Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. Neuropathology 28:62–68

    Article  PubMed  Google Scholar 

  30. Armitage PA, Schwindack C, Bastin ME, Whittle IR (2007) Quantitative assessment of intracranial tumor response to dexamethasone using diffusion, perfusion and permeability magnetic resonance imaging. Magn Reson Imaging 25:303–310

    Article  PubMed  CAS  Google Scholar 

  31. Thoren FB, Romero AI, Hellstrand K (2006) Oxygen radicals induce poly(ADP-ribose) polymerase-dependent cell death in cytotoxic lymphocytes. J Immunol 176:7301–7307

    PubMed  CAS  Google Scholar 

  32. Fulda S, Küfer MU, Meyer E, Van Valen F, Dockhorn-Dworniczak B, Debatin KM (2001) Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 20:5865–5877

    Article  PubMed  CAS  Google Scholar 

  33. Borner C, Monney L (1999) Apoptosis without caspases: an inefficient molecular guillotine? Cell Death Diff 6:497–507

    Article  CAS  Google Scholar 

  34. Sordet O, Rebe C, Plenchette S, Zermati Y, Hermine O, Vainchenker W, Garrido C, Solary E, Dubrez-Daloz L (2002) Specific involvement of caspases in the differentiation of monocytes into macrophages. Blood 100:4446–4453

    Article  PubMed  CAS  Google Scholar 

  35. Banks DP, Plescia J, Altieri DC, Chen J, Rosenberg SH, Zhang H, NG SC (1999) Survivin does not inhibit caspase-3 activity. Blood 96:4002–4003

    Google Scholar 

  36. Zangemeister-Wittke U, Simon HU (2004) An IAP in action: the multiple roles of surviving in differentiation, immunity and malignancy. Cell Cycle 3:1121–1123

    Article  PubMed  CAS  Google Scholar 

  37. Fischer U, Janssen K, Schulze-Osthoff K (2007) Does caspase inhibition promote clonogenic tumor growth? Cell Cycle 6:3048–3053

    Article  PubMed  CAS  Google Scholar 

  38. Al-Khalaf HH, Lach B, Allam A, Hassounah M, Alkhani A, Elkum N, Alrokayan SA, Aboussekhra A (2008) Expression of survivin and p16INK4a/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells. Brain Res 1188:25–34

    Article  PubMed  CAS  Google Scholar 

  39. McLean CA, Jolley D, Cukier E, Giles G, Gonzales MF (1993) Atypical and malignant meningiomas: importance of micronecrosis as a prognostic indicator. Histopathology 33:64–70

    Google Scholar 

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Acknowledgment

This work was supported by grants from “Progetto Ricerca Sanitaria Finalizzata 2007” (prot. 2472/DA2001), PIEDMONT, Italy.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Laboratory of Human Anatomy, University of Eastern Piedmont “A. Avogadro”, Via Solaroli 17, 28100, Novara, Italy

    Maurizio Sabbatini, Valentina Piffanelli & Mario Cannas

  2. Department of Medical Science, Laboratory of Immunology, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

    Annalisa Chiocchetti & Umberto Dianzani

  3. Department of Neurology, University of Eastern Piedmont “A. Avogadro”, Novara, Italy

    Cristoforo Comi & Francesco Monaco

  4. Neurosurgery Division, “Ospedale Maggiore della Carità” of Novara, Novara, Italy

    Pier Giorgio Car

Authors
  1. Maurizio Sabbatini
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  2. Cristoforo Comi
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  3. Annalisa Chiocchetti
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  4. Valentina Piffanelli
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  7. Francesco Monaco
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  8. Mario Cannas
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Correspondence to Maurizio Sabbatini.

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Sabbatini, M., Comi, C., Chiocchetti, A. et al. Signals of Apoptotic Pathways in Several Types of Meningioma. Pathol. Oncol. Res. 17, 51–59 (2011). https://doi.org/10.1007/s12253-010-9279-1

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  • DOI: https://doi.org/10.1007/s12253-010-9279-1

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