Transforming growth factor-beta effects on meningioma cell proliferation and signal transduction pathways.
The role of transforming growth factor-beta (TGF-beta) in regulation of meningioma growth and intracellular events transducing its signals are not established. In this study, we evaluated the effects of TGF-beta1 on basal meningioma cell proliferation in 10 primary human meningioma cell cultures and whether TGF-beta's signals are transduced by the Smad 2/3, MAPK/Erk kinase-1 (MEK-1)-mitogen-activated protein kinase (MAPK), Akt-p70(S6K) or p38-JUNK pathways in 5. We also tested whether neutralizing antibodies to TGF-beta alter CSF stimulation of meningioma cell proliferation. On average, TGF-beta reduced meningioma cell [3H]-thymidine incorporation to 58% of controls at 24% and to 61% of controls at 36 h. TGF-beta inhibition of meningioma cell proliferation was associated with a suggestion increased phosphorylation of Smad 2/3 in 2 cases and high basal phosphorylation in 3 but no change in activation of the MEK-1-MAPK, Akt-p70(S6K) or p38-JUNK pathways. As shown previously, CSF stimulated meningioma cell proliferation in the 3 cultures tested. Neutralizing antibody against TGF-beta augmented this stimulation in 2 of 3 cultures. These findings suggest that TGF-beta exerts a largely inhibitory effect on basal meningioma proliferation, perhaps in part through Smad 2/3.
Johnson
Mahlon D
MD
Department of Pathology, Vanderbilt Medical School, Nashville, TN 37232, USA. mahlon.johnson@mcmail.vanderbilt.edu
Okediji
Evelyn
E
Woodard
Ann
A
D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002555:Cerebrospinal Fluid / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein; D051900:Smad3 Protein; D013936:Thymidine / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D000906:Antibodies; D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013936:Thymidine