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Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1–STAT3, MEK1–p44/42MAPK, Akt–mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from “normal” volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3.

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The authors declare they have no conflicts of interest.

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Authors and Affiliations

  1. Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Box 626, Rochester, NY, 14642, USA

    Mahlon D. Johnson & Mary O’Connell

  2. Division of Cytopathology, Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Michael Facik

  3. Department of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Paul Maurer, Babak Jahromi & Webster Pilcher

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  1. Mahlon D. Johnson
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  2. Mary O’Connell
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  3. Michael Facik
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  4. Paul Maurer
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  5. Babak Jahromi
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  6. Webster Pilcher
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Correspondence to Mahlon D. Johnson.

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Johnson, M.D., O’Connell, M., Facik, M. et al. Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3. J Neurooncol 107, 121–131 (2012). https://doi.org/10.1007/s11060-011-0736-9

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  • DOI: https://doi.org/10.1007/s11060-011-0736-9

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