Radiation effects on human leptomeningeal cell response to cerebrospinal fluid and PDGF-BB

Mahlon Johnson, Mary O'Connell, M. Anwar Iqbal, Jacqueline P. Williams

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: The pathogenesis of meningiomas remains largely unknown, but there is evidence that exposure radiation increases the risk of meningiomas. We therefore evaluated whether radiation stimulates human leptomeningeal cell proliferation and activates growth regulatory pathways. Materials and methods: Cultures from six human primary leptomeningeal cells were established and irradiated with 0.5, 1 or 2 Gy. Cells were subsequently maintained for approximately 36 months and then treated with the mitogen, platlet-derived growth factor-BB (PDGF-BB), or human cerebrospinal fluid (CSF) obtained from patients with no neurological disease. Cell proliferation was evaluated by CyQUANT, and changes in the regulatory activation levels of signal transducer and activator of transcription (STAT3), mitogen-activated protein kinase kinase 1/2 (MEK1/2), mitogen activated protein kinase (MAPK 44/42), Akt, and mammalian target of rapamycin (mTOR) were assessed by Western blot. Results: At both 3 and 6 months post-irradiation, CSF stimulated cell proliferation in all six leptomeningeal cultures. At 3 months, radiation was associated with an increase in STAT3, MEK 1/2, p44/42 MAPK and variable Akt activation, and at 6 months, STAT3, p44/42 MAPK, variable Akt and mTOR activation was observed in response to PDGF-BB and CSF. Conclusions: Irradiation of fetal leptomeningeal cells was associated with loss of heterozygosity of 1p36 and persistent sensitization leading to upregulation in growth pathways in response to PDGF and CSF. These findings suggest a mechanistic basis for radiation's role in meningioma initiation.

Original languageEnglish (US)
Pages (from-to)547-555
Number of pages9
JournalInternational Journal of Radiation Biology
Volume88
Issue number7
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Fingerprint

Radiation Effects
Cerebrospinal Fluid
Intercellular Signaling Peptides and Proteins
Meningioma
Mitogen-Activated Protein Kinase 3
Cell Proliferation
Sirolimus
Radiation
MAP Kinase Kinase 2
MAP Kinase Kinase 1
Loss of Heterozygosity
Mitogen-Activated Protein Kinase Kinases
Growth
Mitogen-Activated Protein Kinases
Transducers
Mitogens
Up-Regulation
Western Blotting

All Science Journal Classification (ASJC) codes

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Radiation effects on human leptomeningeal cell response to cerebrospinal fluid and PDGF-BB. / Johnson, Mahlon; O'Connell, Mary; Iqbal, M. Anwar; Williams, Jacqueline P.

In: International Journal of Radiation Biology, Vol. 88, No. 7, 01.07.2012, p. 547-555.

Research output: Contribution to journalArticle

Johnson, Mahlon ; O'Connell, Mary ; Iqbal, M. Anwar ; Williams, Jacqueline P. / Radiation effects on human leptomeningeal cell response to cerebrospinal fluid and PDGF-BB. In: International Journal of Radiation Biology. 2012 ; Vol. 88, No. 7. pp. 547-555.
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