Analysis of Transforming Growth Factor β Receptor Expression and Signaling in Higher Grade Meningiomas

Overview

Journal J Neurooncol

Publisher Springer

Date 2010 Sep 21

PMID 20853018

Citations 7

Authors

Mahlon D Johnson

Aubie K Shaw

Mary J OConnell

Fraser J Sim

Harold L Moses

Affiliations

Soon will be listed here.

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.

Citing Articles

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Differentially Expressed MicroRNAs in Radioresistant and Radiosensitive Atypical Meningioma: A Clinical Study in Chinese Patients.

Zhang X, Zhang G, Huang H, Li H, Lin S, Wang Y Front Oncol. 2020; 10:501.

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Advances in meningioma genetics: novel therapeutic opportunities.

Preusser M, Brastianos P, Mawrin C Nat Rev Neurol. 2018; 14(2):106-115.

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