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

  • Laboratory Investigation - Human/Animal Tissue
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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.

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Authors and Affiliations

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

    Mahlon D. Johnson & Mary J. O’Connell

  2. Center for Translational Neuromedicine, Department of Neurology, University of Rochester School of Medicine, University of Rochester Medical Center, Rochester, NY, USA

    Fraser J. Sim

  3. Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA

    Aubie K. Shaw & Harold L. Moses

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  1. Mahlon D. Johnson
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Correspondence to Mahlon D. Johnson.

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Johnson, M.D., Shaw, A.K., O’Connell, M.J. et al. Analysis of transforming growth factor β receptor expression and signaling in higher grade meningiomas. J Neurooncol 103, 277–285 (2011). https://doi.org/10.1007/s11060-010-0399-y

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  • DOI: https://doi.org/10.1007/s11060-010-0399-y

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