Authors: Mahlon D Johnson Aubie K Shaw Mary J O’Connell Fraser J Sim Harold L Moses
Publish Date: 2010/09/19
Volume: 103, Issue: 2, Pages: 277-285
Abstract
TGFβ receptors TGFβRs inhibit growth of many cell types Loss of TGFβRs or its signaling components have been found in several human malignancies The expression and the role of TGFβRs in regulating anaplastic meningioma growth has not been studied Real time PCR found TGFβ RIII expression significantly lower in five grade III compared to eight grade I and eight grade II tumors P = 00481 By western blot analysis TGFβRI was detected in the four fetal and adult leptomeninges all 18 grade I 14 grade II and six grade III meningiomas TGFβRII 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 TGFβRIII 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 PhosphoSMAD 3 and Smad 7 were detected in nearly all tumors TGFβ1 had no effect on PDGFBB 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 TGFβRIII expression and TGFB growth inhibition may occur in select higher grade meningiomas Nonetheless restoring TGFβ inhibition of meningioma cell proliferation may be an important objective in the design of new chemotherapies for these tumors
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