Expression of TGF-beta isoforms, TGF-beta receptors, and Smad molecules atdifferent stages of human glioma

Human gliomas express TGF-beta but, so far the expression of downstream med iators has been investigated in only a few cell lines. We have examined tis sue specimens of 23 gliomas: 3 astrocytomas grade II (AST), 8 anaplastic as trocytomas grade III (AAST), and 12 glioblastoma multiforme grade IV (GBM), We analyzed the mRNA expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, the TGF-beta receptors type I (T beta R-I) and type II (T beta R-II), Smad2, S mad3, and Smad4, mRNA expression of IL-10 and CD95 (FAS/APO-1) were also st udied. We detected increased mRNA levels of the 3 TGF-beta isoforms, correl ating with the degree of malignancy. TGF-beta 3 mRNA was increased, particu larly in AST and AAST, while TGF-beta 1 and TGF-beta 2 mRNAs were strongly expressed in GEM. TGF-beta normally up-regulates the TGF-beta receptors, an d T beta R-1 and T beta R-II showed stronger expression in all gliomas when compared to normal tissues. However, the mRNA expression of Smad2, Smad3, and Smad4 was decreased in GEM. IL-10 mRNA expression was detected in gliom a tissues but not in glioma cell lines. No marked increase in the expressio n of soluble CD95 splicing variants was found in the gliomas compared with normal tissue. However, total CD95 mRNA was elevated among GBM tissues. (C) 2000 Wiley-Liss, Inc.