Expression of transforming-growth-factor (TGF)-beta receptors and Smad proteins in glioblastoma cell lines with distinct responses to TGF-beta 1

A panel of 6 human glioma cell lines was examined for TGF-beta 1responsiven ess. U-178 MG and U-251 MG AgC11 were significantly inhibited by TGF-beta 1 while U-343 MGa31L and U-343 MGa35L were potently stimulated to proliferat e. TGF-beta 1 induced endogenous PAI-1 protein synthesis, Smad binding elem ent/(CAGA)(12)-luciferase-reporter activity, as well as mRNA expression of Smad6 and Smad7 in all gliomas. Interestingly, TGF-beta 1 differentially st imulated or inhibited the expression of T beta R-I and T beta R-II mRNA in the gliomas, Affinity cross-linking studies using I-125-TGF-beta 1 revealed that the gliomas expressed TGF-beta-type-I(T beta R-1) and -type-II(T beta R-II) receptors, although binding to T beta R-II in U-343 MGa31L and U-251 MG AgCI1 was low to undetectable, Smad2 protein was abundantly present in U-178 MG, U-343 MG, and U-343 MGa35L, while Smad3 was readily detectable in U-178 MG, U-343 MG, U-343 MGa35L and U-251 MG AgC11. In all gliomas, TGF-b eta 1 induced phosphorylation of Smad2. The level to which TGF-beta 1 could activate the pathway leading to induction of the (CAGA)(12)-luciferase rep orter seemed to correlate to the expression levels of TGF-beta receptors, S mad3 and Smad4 proteins. However, despite the plethora of data regarding TG F-beta 1 signalling in the different glioma cell lines, the mechanism under lying the differential growth effects mediated by TGF-beta 1 is still uncle ar. The results suggest that a complex balance between several components i n the TGF-beta signalling pathway controls glioma responsiveness to TGF-bet a 1, and extend reports indicating that distinct signal transduction pathwa ys are involved in growth inhibition and other cellular responses. Int. J. Cancer 80:756-763, 1999. (C) 1999 Wiley-Liss, Inc.