科研之友
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摘要
TGF-beta receptors (TGF-beta Rs) inhibit growth of many cell types. Loss of TGF-beta Rs or its signaling components have been found in several human malignancies. The expression and the role of TGF-beta Rs in regulating anaplastic meningioma growth has not been studied. Real time PCR found TGF-beta 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-beta RI was detected in the four fetal and adult leptomeninges, all 18 grade I, 14 grade II and six grade III meningiomas. TGF-beta RII 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-beta RIII 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-beta 1 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-beta RIII expression and TGFB growth inhibition may occur in select higher grade meningiomas. Nonetheless, restoring TGF-beta inhibition of meningioma cell proliferation may be an important objective in the design of new chemotherapies for these tumors.
- 出版日期2011-6
