Expression of TGF-β isoforms, TGF-β receptors, and SMAD molecules at different stages of human glioma

Abstract

Human gliomas express TGF-β but, so far the expression of downstream mediators has been investigated in only a few cell lines. We have examined tissue specimens of 23 gliomas: 3 astrocytomas grade II (AST), 8 anaplastic astrocytomas grade III (AAST), and 12 glioblastoma multiforme grade IV (GBM). We analyzed the mRNA expression of TGF-β1, TGF-β2, TGF-β3, the TGF-β receptors type I (TβR-I) and type II (TβR-II), Smad2, Smad3, and Smad4. mRNA expression of IL-10 and CD95 (FAS/APO-1) were also studied. We detected increased mRNA levels of the 3 TGF-β isoforms, correlating with the degree of malignancy. TGF-β3 mRNA was increased, particularly in AST and AAST, while TGF-β1 and TGF-β2 mRNAs were strongly expressed in GBM. TGF-β normally up-regulates the TGF-β receptors, and TβR-I and TβR-II showed stronger expression in all gliomas when compared to normal tissues. However, the mRNA expression of Smad2, Smad3, and Smad4 was decreased in GBM. IL-10 mRNA expression was detected in glioma tissues but not in glioma cell lines. No marked increase in the expression of soluble CD95 splicing variants was found in the gliomas compared with normal tissue. However, total CD95 mRNA was elevated among GBM tissues. Int. J. Cancer 89:251–258, 2000.