Analysis of transforming growth factor β receptor expression and signaling in higher grade meningiomas.
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.
Johnson
Mahlon D
MD
Department of Pathology, Division of Neuropathology, University of Rochester Medical Center, 601 Elmwood Ave. Box 626, Rochester, NY 14642, USA. mahlon_johnson@urmc.rochester.edu
Shaw
Aubie K
AK
O'Connell
Mary J
MJ
Sim
Fraser J
FJ
Moses
Harold L
HL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta