ENHANCED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA AND ITS TYPE-IAND TYPE-II RECEPTORS IN HUMAN GLIOBLASTOMA

Immunohistochemical studies of transforming growth factor-beta (TGF-be ta) and its receptors have been carried out on 16 glioma tissues and c ompared with 5 cases of gliosis. Significantly higher expressions of T GF-beta I, as well as type-I and type-II TGF-beta receptors (T beta R- I and T beta R-II, respectively), were observed in advanced-malignant- glioma tissues when compared with non-tumorous gliosis. Immunoreactivi ties of TGF-beta and T beta R-I were localized in the cytoplasm of spi ndle-shaped tumor cells surrounding proliferating vessels or around ar eas of necrosis. The advancing edge of the tumor clusters frequently s tained positive. Similar expression patterns were found for TGF-beta 2 and TGF-beta 3, whereas only weak or no expression was found for endo glin. In low-grade astrocytomas and in gliosis cases, the expression w as moderate for T beta R-I and weak for TGF-beta and T beta R-II. In 3 examined human malignant glioma cell lines, clear immunostainings wer e detected for TGF-beta and its receptors. Ligand-induced heteromeric complexes of the receptors were formed in these cell lines, but the am ount of the receptors was less than that of mink lung epithelial cells , which are sensitive target cells for TGF-beta. TGF-beta I showed no growth-inhibitory activity on any of these glioma cell lines. These re sults suggest that malignant gliomas produce TCF-beta and receptors, b ut are refractory to TGF-beta, implying dysregulation in the signallin g pathway in the tumor cells. It is possible that the released TGF-bet a acts on neighboring cells and affects stromal growth, angiogenesis, metastasis or immune surveillance in human glioma. (C) 1995 Wiley-Liss , Inc.