Journal of Neuro-Oncology

, Volume 99, Issue 3, pp 325–331

Meningioma mouse models

  • Michel Kalamarides
  • Matthieu Peyre
  • Marco Giovannini
Invited Review

Abstract

Meningiomas, although mostly benign, may sometimes present aggressive features and raise issues concerning alternative treatment options besides surgery. In order to gain new insights in meningioma biology and develop alternative treatments, several meningioma mouse models have been engineered during the past two decades. As rodents very rarely develop spontaneous meningiomas, animal models have been first developed by implanting human meningioma cells derived from a primary tumor and meningioma cell lines subcutaneously into athymic mice. Induction of de novo meningiomas in rodents with mutagens, such as nitrosourea, has also been reported. Advances in our understanding of molecular genetics of meningioma have pinpointed the central role of NF2 tumor suppressor gene in the pathogenesis of those tumors. These discoveries have led to the creation of a genetically engineered model utilizing conditional mutagenesis to specifically inactivate the mouse Nf2 gene in arachnoidal cells, resulting in the formation of intracranial meningothelial hyperplasia and meningiomas and thus reproducing the main mechanism of human meningeal tumorigenesis. This powerful new technology significantly improves on prior models and may open avenues of investigation never before possible in meningioma research. We present here a review of current meningioma mouse models used in translational therapeutics with associated imaging and pre-clinical studies.

Keywords

Brain tumor NF2 Arachnoid Transgenic mice Mouse model 

References

  1. 1.
    Aghi MK, Carter BS, Cosgrove GR et al (2009) Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation. Neurosurgery 64:56–60 discussion 60CrossRefPubMedGoogle Scholar
  2. 2.
    Yang SY, Park CK, Park SH et al (2008) Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features. J Neurol Neurosurg Psychiatry 79:574–580CrossRefPubMedGoogle Scholar
  3. 3.
    Evans DG, Huson SM, Donnai D et al (1992) A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29:841–846CrossRefPubMedGoogle Scholar
  4. 4.
    Gutmann DH, Giordano MJ, Fishback AS, Guha A (1997) Loss of merlin expression in sporadic meningiomas, ependymomas and schwannomas. Neurology 49:267–270PubMedGoogle Scholar
  5. 5.
    Perry A, Cai DX, Scheithauer BW et al (2000) Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases. J Neuropathol Exp Neurol 59:872–879PubMedGoogle Scholar
  6. 6.
    Lee WH (1990) Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-Lee. Neurosurgery 27:389–395 discussion 396CrossRefPubMedGoogle Scholar
  7. 7.
    Tsai JC, Goldman CK, Gillespie GY (1995) Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg 82:864–873CrossRefPubMedGoogle Scholar
  8. 8.
    Ragel BT, Couldwell WT, Gillespie DL et al (2008) A comparison of the cell lines used in meningioma research. Surg Neurol 70:295–307 discussion 307CrossRefPubMedGoogle Scholar
  9. 9.
    Sasaki M, Honda T, Yamada H et al (1994) Evidence for multiple pathways to cellular senescence. Cancer Res 54:6090–6093PubMedGoogle Scholar
  10. 10.
    Leuraud P, Dezamis E, Aguirre-Cruz L et al (2004) Prognostic value of allelic losses and telomerase activity in meningiomas. J Neurosurg 100:303–309CrossRefPubMedGoogle Scholar
  11. 11.
    Langford LA, Piatyszek MA, Xu R et al (1997) Telomerase activity in ordinary meningiomas predicts poor outcome. Hum Pathol 28:416–420CrossRefPubMedGoogle Scholar
  12. 12.
    Boldrini L, Pistolesi S, Gisfredi S et al (2003) Telomerase in intracranial meningiomas. Int J Mol Med 12:943–947PubMedGoogle Scholar
  13. 13.
    Maes L, Lippens E, Kalala JP, de Ridder L (2005) The hTERT-protein and Ki-67 labelling index in recurrent and non-recurrent meningiomas. Cell Prolif 38:3–12CrossRefPubMedGoogle Scholar
  14. 14.
    Baia GS, Slocum AL, Hyer JD et al (2006) A genetic strategy to overcome the senescence of primary meningioma cell cultures. J Neurooncol 78:113–121CrossRefPubMedGoogle Scholar
  15. 15.
    Cargioli TG, Ugur HC, Ramakrishna N et al (2007) Establishment of an in vivo meningioma model with human telomerase reverse transcriptase. Neurosurgery 60:750–759 discussion 759–760CrossRefPubMedGoogle Scholar
  16. 16.
    Puttmann S, Senner V, Braune S et al (2005) Establishment of a benign meningioma cell line by hTERT-mediated immortalization. Lab Invest 85:1163–1171CrossRefPubMedGoogle Scholar
  17. 17.
    Greene HSN, Arnold H (1945) The homologous and heterologous transplantation of brain and brain tumors. J Neurosurg 2:315–329CrossRefGoogle Scholar
  18. 18.
    Rana MW, Pinkerton H, Thornton H, Nagy D (1977) Heterotransplantation of human glioblastoma multiforme and meningioma to nude mice. Proc Soc Exp Biol Med 155:85–88PubMedGoogle Scholar
  19. 19.
    Ueyama Y, Morita K, Ochiai C et al (1978) Xenotransplantation of a human meningioma and its lung metastasis in nude mice. Br J Cancer 37:644–647PubMedGoogle Scholar
  20. 20.
    Medhkour A, Van Roey M, Sobel RA et al (1989) Implantation of human meningiomas into the subrenal capsule of the nude mouse. A model for studies of tumor growth. J Neurosurg 71:545–550CrossRefPubMedGoogle Scholar
  21. 21.
    Jensen RL, Leppla D, Rokosz N, Wurster RD (1998) Matrigel augments xenograft transplantation of meningioma cells into athymic mice. Neurosurgery 42:130–135 discussion 135–136CrossRefPubMedGoogle Scholar
  22. 22.
    Malham GM, Thomsen RJ, Synek BJ, Baguley BC (2001) Establishment of primary human meningiomas as subcutaneous xenografts in mice. Br J Neurosurg 15:328–334CrossRefPubMedGoogle Scholar
  23. 23.
    McCutcheon IE, Friend KE, Gerdes TM et al (2000) Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth. J Neurosurg 92:306–314CrossRefPubMedGoogle Scholar
  24. 24.
    van Furth WR, Laughlin S, Taylor MD et al (2003) Imaging of murine brain tumors using a 1.5 Tesla clinical MRI system. Can J Neurol Sci 30:326–332PubMedGoogle Scholar
  25. 25.
    Baia GS, Dinca EB, Ozawa T et al (2008) An orthotopic skull base model of malignant meningioma. Brain Pathol 18:172–179CrossRefPubMedGoogle Scholar
  26. 26.
    Ragel BT, Elam IL, Gillespie DL et al (2008) A novel model of intracranial meningioma in mice using luciferase-expressing meningioma cells. Laboratory investigation. J Neurosurg 108:304–310CrossRefPubMedGoogle Scholar
  27. 27.
    McCutcheon IE, Flyvbjerg A, Hill H et al (2001) Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice. J Neurosurg 94:487–492CrossRefPubMedGoogle Scholar
  28. 28.
    Salhia B, Rutka JT, Lingwood C, Nutikka A, Van Furth WR (2002) The treatment of malignant meningioma with verotoxin. Neoplasia 4:304–311CrossRefPubMedGoogle Scholar
  29. 29.
    Gupta V, Su YS, Samuelson CG et al (2007) Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas. J Neurosurg 106:455–462CrossRefPubMedGoogle Scholar
  30. 30.
    Ragel BT, Jensen RL, Gillespie DL, Prescott SM, Couldwell WT (2007) Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. Cancer 109:588–597CrossRefPubMedGoogle Scholar
  31. 31.
    Olson JJ, Beck DW, Schlechte JA, Loh PM (1987) Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice. J Neurosurg 66:584–587CrossRefPubMedGoogle Scholar
  32. 32.
    Jensen RL, Wurster RD (2001) Calcium channel antagonists inhibit growth of subcutaneous xenograft meningiomas in nude mice. Surg Neurol 55:275–283CrossRefPubMedGoogle Scholar
  33. 33.
    Chamberlain MC, Tsao-Wei DD, Groshen S (2004) Temozolomide for treatment-resistant recurrent meningioma. Neurology 62:1210–1212PubMedGoogle Scholar
  34. 34.
    Rice JM, Wilbourn JD (2000) Tumors of the nervous system in carcinogenic hazard identification. Toxicol Pathol 28:202–214CrossRefPubMedGoogle Scholar
  35. 35.
    Morrison JP, Satoh H, Foley J et al (2007) N-ethyl-N-nitrosourea (ENU)-induced meningiomatosis and meningioma in p16(INK4a)/p19(ARF) tumor suppressor gene-deficient mice. Toxicol Pathol 35:780–787CrossRefPubMedGoogle Scholar
  36. 36.
    Avellino AM, Hair LS, Symmans WF et al (1994) Meningeal meningiomatosis in a child: case report. Clin Neuropathol 13:82–87PubMedGoogle Scholar
  37. 37.
    Wakabayashi K, Kawasaki K, Ono K et al (1997) Primary leptomeningeal meningiomatosis with widespread whorl formation. Brain Tumor Pathol 14:139–143CrossRefPubMedGoogle Scholar
  38. 38.
    Balme E, Roth DR, Perentes E (2008) Cerebral meningioangiomatosis in a CD-1 mouse: a case report and comparison with humans and dogs. Exp Toxicol Pathol 60:247–251CrossRefPubMedGoogle Scholar
  39. 39.
    Perry A, Kurtkaya-Yapicier O, Scheithauer BW et al (2005) Insights into meningioangiomatosis with and without meningioma: a clinicopathologic and genetic series of 24 cases with review of the literature. Brain Pathol 15:55–65CrossRefPubMedGoogle Scholar
  40. 40.
    Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–512CrossRefPubMedGoogle Scholar
  41. 41.
    Ramirez-Solis R, Liu P, Bradley A (1995) Chromosome engineering in mice. Nature 378:720–724CrossRefPubMedGoogle Scholar
  42. 42.
    McClatchey AI, Saotome I, Mercer K et al (1998) Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 12:1121–1133CrossRefPubMedGoogle Scholar
  43. 43.
    Giovannini M, Robanus-Maandag E, van der Valk M et al (2000) Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev 14:1617–1630PubMedGoogle Scholar
  44. 44.
    Kalamarides M, Niwa-Kawakita M, Leblois H et al (2002) Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse. Genes Dev 16:1060–1065CrossRefPubMedGoogle Scholar
  45. 45.
    Yamashima T, Sakuda K, Tohma Y et al (1997) Prostaglandin D synthase (beta-trace) in human arachnoid and meningioma cells: roles as a cell marker or in cerebrospinal fluid absorption, tumorigenesis, and calcification process. J Neurosci 17:2376–2382PubMedGoogle Scholar
  46. 46.
    Kawashima M, Suzuki SO, Yamashima T, Fukui M, Iwaki T (2001) Prostaglandin D synthase (beta-trace) in meningeal hemangiopericytoma. Mod Pathol 14:197–201CrossRefPubMedGoogle Scholar
  47. 47.
    Kalamarides M, Stemmer-Rachamimov AO, Takahashi M et al (2008) Natural history of meningioma development in mice reveals: a synergy of Nf2 and p16(Ink4a) mutations. Brain Pathol 18:62–70CrossRefPubMedGoogle Scholar
  48. 48.
    Simon M, Bostrom JP, Hartmann C (2007) Molecular genetics of meningiomas: from basic research to potential clinical applications. Neurosurgery 60:787–798 discussion 787–798CrossRefPubMedGoogle Scholar
  49. 49.
    Bostrom J, Meyer-Puttlitz B, Wolter M et al (2001) Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. Am J Pathol 159:661–669PubMedGoogle Scholar
  50. 50.
    Perry A, Banerjee R, Lohse CM, Kleinschmidt-DeMasters BK, Scheithauer BW (2002) A role for chromosome 9p21 deletions in the malignant progression of meningiomas and the prognosis of anaplastic meningiomas. Brain Pathol 12:183–190PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Michel Kalamarides
    • 1
    • 2
    • 3
  • Matthieu Peyre
    • 1
    • 2
    • 3
  • Marco Giovannini
    • 4
  1. 1.Department of NeurosurgeryAPHP, Hopital Beaujon, Service de NeurochirurgieClichyFrance
  2. 2.Inserm, U674ParisFrance
  3. 3.Université Paris 7-Denis Diderot, Institut Universitaire d’hématologieParisFrance
  4. 4.House Ear Institute, Center for Neural Tumor ResearchLos AngelesUSA

Personalised recommendations