Skip to main content
SpringerLink
Log in

A genetic strategy to overcome the senescence of primary meningioma cell cultures

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Even though meningiomas are the second most common brain tumor in adults, little is known about the molecular basis of their growth and development. The lack of suitable cell culture model systems is an impediment to this understanding. Most studies on meningiomas rely on primary, early passage cell lines that eventually senesce or a few established cell lines that have been derived from aggressive variants of meningiomas. We have isolated three primary meningioma cell lines that are negative for telomerase activity. We can overcome the senescence of a Grade III derived meningioma cell line by expressing the telomerase catalytic subunit (hTERT), whereas Grade I meningioma cell lines require the expression of the human papillomavirus E6 and E7 oncogenes in conjunction with hTERT. Meningioma cell lines, immortalized in this manner, maintain their pre-transfection morphology and form colonies in vitro. We have confirmed the meningothelial origin of these cell lines by assessing expression of vimentin and desmoplakin, characteristic markers for meningiomas. Additionally, we have karyotyped these cell lines using array CGH and shown that they represent a spectrum of the genetic diversity seen in primary meningiomas. Thus, these cell lines represent novel cellular reagents for investigating the molecular oncogenesis of meningiomas.

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

Similar content being viewed by others

References

  1. Lusis E, Gutmann DH (2004) Meningioma: an updateCurr Opin Neurol 17:687–692

    Article  PubMed  Google Scholar 

  2. Puduvalli VK, Li JT, Chen L, McCutcheon IE (2005) Induction of apoptosis in primary meningioma cultures by fenretinideCancer Res 65:1547–1553

    Article  PubMed  CAS  Google Scholar 

  3. Dirven CM, Grill J, Lamfers ML, Van der Valk P, Leonhart AM, Van Beusechem VW, Haisma HJ, Pinedo HM, Curiel DT, Vandertop WP, Gerritsen WR (2002) Gene therapy for meningioma: improved gene delivery with targeted adenovirusesJ Neurosurg 97:441–449

    PubMed  CAS  Google Scholar 

  4. Ikeda K, Saeki Y, Gonzalez-Agosti C, Ramesh V, Chiocca EA (1999) Inhibition of NF2-negative and NF2-positive primary human meningioma cell proliferation by overexpression of merlin due to vector-mediated gene transferJ Neurosurg 91:85–92

    PubMed  CAS  Google Scholar 

  5. Shu J, Lee JH, Harwalkar JA, Oh-Siskovic S, Stacey DW, Golubic M (1999) Adenovirus-mediated gene transfer of dominant negative Ha-Ras inhibits proliferation of primary meningioma cellsNeurosurgery 44:579–587

    Article  PubMed  CAS  Google Scholar 

  6. Lee WH, (1990) Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-LeeNeurosurgery 27:389–395

    Article  PubMed  CAS  Google Scholar 

  7. Tanaka K, Sato C, Maeda Y, Koike M, Matsutani M, Yamada K, Miyaki M (1989) Establishment of a human malignant meningioma cell line with amplified c-myc oncogeneCancer 64:2243–2249

    Article  PubMed  CAS  Google Scholar 

  8. Sasaki M, Honda T, Yamada H, Wake N, Barrett JC, Oshimura M (1994) Evidence for multiple pathways to cellular senescenceCancer Res 54:6090–6093

    PubMed  CAS  Google Scholar 

  9. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR (1995) Telomere elongation in immortal human cells without detectable telomerase activityEMBO J 14:4240–4248

    PubMed  CAS  Google Scholar 

  10. Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR (1997) Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell linesNat Med 3:1271–1274

    Article  PubMed  CAS  Google Scholar 

  11. Campisi J, (2001) Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 11:S27–S31

    PubMed  CAS  Google Scholar 

  12. Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA, Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cellsNature 396:84–88

    Article  PubMed  CAS  Google Scholar 

  13. Gupta N, Lamborn K, Deen DF (1996) A statistical approach for analyzing clonogenic survival dataRadiat Res 145:636–640

    Article  PubMed  CAS  Google Scholar 

  14. Cuevas IC, Slocum AL, Jun P, Costello JF, Bollen AW, Riggins GJ, McDermott MW, Lal A (2005) Meningioma transcript profiles reveal deregulated notch signaling pathwayCancer Res 65:5070–5075

    Article  PubMed  CAS  Google Scholar 

  15. Snijders AM, Nowak N, Segraves R, Blackwood S, Brown N, Conroy J, Hamilton G, Hindle AK, Huey B, Kimura K, Law S, Myambo K, Palmer J, Ylstra B, Yue JP, Gray JW, Jain AN, Pinkel D, Albertson DG (2001) Assembly of microarrays for genome-wide measurement of DNA copy numberNat Genet 29:263–264

    Article  PubMed  CAS  Google Scholar 

  16. Jain AN, Tokuyasu TA, Snijders AM, Segraves R, Albertson DG, Pinkel D (2002) Fully automatic quantification of microarray image dataGenome Res 12:325–332

    Article  PubMed  CAS  Google Scholar 

  17. Howley PM, Munger K, Romanczuk H, Scheffner M, Huibregtse JM (1991) Cellular targets of the oncoproteins encoded by the cancer associated human papillomavirusesPrincess Takamatsu Symp 22:239–248

    PubMed  CAS  Google Scholar 

  18. Bostrom J, Meyer-Puttlitz B, Wolter M, Blaschke B, Weber RG, Lichter P, Ichimura K, Collins VP, Reifenberger G (2001) Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomasAm J Pathol 159:661–669

    PubMed  CAS  Google Scholar 

  19. Ducrest AL, Amacker M, Mathieu YD, Cuthbert AP, Trott DA, Newbold RF, Nabholz M, Lingner J (2001) Regulation of human telomerase activity: repression by normal chromosome 3 abolishes nuclear telomerase reverse transcriptase transcripts but does not affect c-Myc activityCancer Res 61:7594–7602

    PubMed  CAS  Google Scholar 

  20. Evans RM (1998) Vimentin: the conundrum of the intermediate filament gene familyBioessays 20:79–86

    Article  PubMed  CAS  Google Scholar 

  21. Burdett ID (1998) Aspects of the structure and assembly of desmosomesMicron 29:309–328

    Article  PubMed  CAS  Google Scholar 

  22. Akat K, Mennel HD, Kremer P, Gassler N, Bleck CK, Kartenbeck J (2003) Molecular characterization of desmosomes in meningiomas and arachnoidal tissueActa Neuropathol (Berl) 106:337–347

    Article  CAS  Google Scholar 

  23. Hodgson G, Hager JH, Volik S, Hariono S, Wernick M, Moore D, Nowak N, Albertson DG, Pinkel D, Collins C, Hanahan D, Gray JW (2001) Genome scanning with array CGH delineates regional alterations in mouse islet carcinomasNat Genet 29:459–464

    Article  PubMed  CAS  Google Scholar 

  24. Misra A, Pellarin M, Nigro J, Smirnov I, Moore D, Lamborn KR, Pinkel D, Albertson DG, Feuerstein BG (2005) Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytomaClin Cancer Res 11:2907–2918

    Article  PubMed  CAS  Google Scholar 

  25. De Vitis LR, Tedde A, Vitelli F, Ammannati F, Mennonna P, Bigozzi U, Montali E, Papi L (1996) Screening for mutations in the neurofibromatosis type 2 (NF2) gene in sporadic meningiomasHum Genet 97:632–637

    Article  PubMed  Google Scholar 

  26. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA (1999) Creation of human tumour cells with defined genetic elementsNature 400:464–468

    Article  PubMed  CAS  Google Scholar 

  27. Sonoda Y, Ozawa T, Hirose Y, Aldape KD, McMahon M, Berger MS, Pieper RO (2001) Formation of intracranial tumors by genetically modified human astrocytes defines four pathways critical in the development of human anaplastic astrocytomaCancer Res 61:4956–4960

    PubMed  CAS  Google Scholar 

  28. Leuraud P, Dezamis E, Aguirre-Cruz L, Taillibert S, Lejeune J, Robin E, Mokhtari K, Boch AL, Cornu P, Delattre JY, Sanson M (2004) Prognostic value of allelic losses and telomerase activity in meningiomasJ Neurosurg 100:303–309

    Article  PubMed  CAS  Google Scholar 

  29. Simon M, Park TW, Leuenroth S, Hans VH, Loning T, Schramm J (2003) Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progressionJ Neurosurg 92:832–840

    Google Scholar 

  30. Ducrest AL, Szutorisz H, Lingner J, Nabholz M (2002) Regulation of the human telomerase reverse transcriptase geneOncogene 21:541–552

    Article  PubMed  CAS  Google Scholar 

  31. Puttmann S, Senner V, Braune S, Hillmann B, Exeler R, Rickert CH, Paulus W Establishment of a benign meningioma cell line by hTERT-mediated immortalization Lab Invest 85 2005 1163–1171

    Article  PubMed  CAS  Google Scholar 

  32. Simon M, Park TW, Koster G, Mahlberg R, Hackenbroch M, Bostrom J, Loning T, Schramm J (2001) Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progressionJ Neurooncol 55:149–158

    Article  PubMed  CAS  Google Scholar 

  33. Carlson KM, Bruder C, Nordenskjold M, Dumanski JP (1997) 1p and 3p deletions in meningiomas without detectable aberrations of chromosome 22 identified by comparative genomic hybridizationGenes Chromosomes Cancer 20:419–424

    Article  PubMed  CAS  Google Scholar 

  34. Smith ML, Fornace AJ (1995) Genomic instability and the role of p53 mutations in cancer cellsCurr Opin Oncol 7:69–75

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Russell O Pieper for retroviral constructs for telomerase and the human papillomavirus E6 and E7 oncogenes and the Neurological Surgery Tissue Bank at University of California, San Francisco for providing viable meningioma tumor samples. A.L. is a recipient of The Sontag Foundation Distinguished Scientist Award. This research was supported in part by The Sontag Foundation.

Author information

Authors and Affiliations

  1. Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA

    Gilson S. Baia, Alison L. Slocum, Jeanette D. Hyer, Anjan Misra, Nouzhan Sehati, Scott R. VandenBerg, Burt G. Feuerstein, Dennis F. Deen, Michael W. McDermott & Anita Lal

  2. Department of Pathology, University of California, San Francisco, CA, 94143, USA

    Scott R. VandenBerg

  3. Department of Laboratory Medicine, University of California, 94143, San Francisco, CA, USA

    Burt G. Feuerstein

  4. Brain Tumor Research Center, Department of Neurological Surgery, University of California, Box 0520, San Francisco, CA, 94143, USA

    Anita Lal

Authors
  1. Gilson S. Baia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alison L. Slocum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeanette D. Hyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anjan Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nouzhan Sehati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott R. VandenBerg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Burt G. Feuerstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dennis F. Deen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael W. McDermott
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Anita Lal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anita Lal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baia, G.S., Slocum, A.L., Hyer, J.D. et al. A genetic strategy to overcome the senescence of primary meningioma cell cultures. J Neurooncol 78, 113–121 (2006). https://doi.org/10.1007/s11060-005-9076-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-005-9076-y

Keywords

Search

Navigation