Analysis of transforming growth factor β receptor expression and signaling in higher grade meningiomas

Mahlon D. Johnson, Aubie K. Shaw, Mary J. O'Connell, Fraser J. Sim, Harold L. Moses

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

TGF-β receptors (TGF-βRs) inhibit growth of many cell types. Loss of TGF-βRs or its signaling components have been found in several human malignancies. The expression and the role of TGF-βRs in regulating anaplastic meningioma growth has not been studied. Real time PCR found TGF-β RIII expression significantly lower in five grade III compared to eight grade I and eight grade II tumors (P = 0.0481). By western blot analysis, TGF-βRI was detected in the four fetal and adult leptomeninges, all 18 grade I, 14 grade II and six grade III meningiomas. TGF-βRII was detected in none of the leptomeninges, 55% of grade I, 71% of grade II and weak to negative in five of six the grade III meningiomas analyzed. TGF-βRIII immunoreactivity was not detected in the fetal meninges but was detected in 94% of grade I, 70% of grade II and 67% grade III tumors. Phospho-SMAD 3 and Smad 7 were detected in nearly all tumors. TGF-β1 had no effect on PDGF-BB stimulation of DNA synthesis in six of seven WHO grade II and the grade III cells. It produced an increase in phosphorylation of SMAD 3 and p38MAPK in two of four and p44/42MAPK in three of four grade II cells showing no change in DNA synthesis after treatment. Thus, only attenuated TGF-βRIII expression and TGFB growth inhibition may occur in select higher grade meningiomas. Nonetheless, restoring TGF-β inhibition of meningioma cell proliferation may be an important objective in the design of new chemotherapies for these tumors.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalJournal of neuro-oncology
Volume103
Issue number2
DOIs
StatePublished - Jun 2011

Keywords

  • Anaplastic meningioma
  • MAPK
  • Meningioma
  • SMAD 3
  • TGF-β
  • TGF-β receptors

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