Transforming growth factors beta(1) (TGF-beta(1)) and TGF-beta(2) promote glioma cell migration via Up-regulation of alpha(V)beta(3) integrin expression.
The migratory behaviour of malignant gliomas relies on the interaction of integrins with extracellular matrix (ECM) components. Transforming growth factor-beta(1) (TGF-beta(1)) potently stimulates glioma cell motility whereas TGF-beta(2) is known for its immunosuppressive properties. Here, we show that both TGF-beta(1) and TGF-beta(2) promote migration of glioma cells. In parallel, TGF-beta(1) and TGF-beta(2) induce alpha(V) and beta(3) intergrin mRNA expression and enhance cell surface expression of alpha(V)beta(3) integrin. TGF-beta-mediated promotion of migration is abrogated by echistatin, a Arg-Gly-Asp (RGD) peptide antagonist of alpha(V)beta(3) integrin, and by a neutralizing anti-alpha(V)beta(3) integrin antibody. Taken together, we report a novel mechanism by which TGF-beta modulates cell ECM interactions and promotes glioma cell motility.
Platten
M
M
Department of Neurology, University of Tübingen Medical School, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany.
Wick
W
W
Wild-Bode
C
C
Aulwurm
S
S
Dichgans
J
J
Weller
M
M
D002465:Cell Movement; D005786:Gene Expression Regulation; D005910:Glioma / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C057986:echistatin