In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We
Enhanced expression of transforming growth factor-β and its type-I and type-II receptors in human glioblastoma
✍ Scribed by Naoshi Yamada; Mitsuyasu Kato; Hidetoshi Yamashita; Monica Nistér; Kohei Miyazono; Carl-Henrik Heldin; Keiko Funa
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 889 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
lmmunohistochemical studies of transforming growth factor$ (TGF-P) and its receptors have been carried out on 16 glioma tissues and compared with 5 cases of gliosis. Significantly higher expressions of TGF-PI, as well as type-I and type4 TGF-fl receptors (TpR-I and TPR-II, respectively), were observed in advanced-malignant-glioma tissues when compared with non-tumorous gliosis. lmmunoreactivities of TGF-fi and TPR-I were localized in the cytoplasm of spindle-shaped tumor cells surrounding proliferating vessels or around areas of necrosis. The advancing edge of the tumor clusters frequently stained positive. Similar expression patterns were found for TGF-P2 and TGF-P3. whereas only weak or no expression was found for endoglin. In low-grade astrocytomas and in gliosis cases, the expression was moderate for TPR-I and weak for TGF-P and TPR-II. In 3 examined human malignant glioma cell lines, clear immunostainings were detected for TGF-P and its receptors. Ligand-induced heteromeric complexes of the receptors were formed in these cell lines, but the amount of the receptors was less than that of mink lung epithelial cells, which are sensitive target cells for TGF-P. TGF-PI showed no growth-inhibitory activity on any of these glioma cell lines. These results suggest that malignant gliomas produce TGF-P and receptors, but are refractory to TGF-P, implying dysregulation in the signalling pathway in the tumor cells. It is possible that the released TGF-P acts on neighboring cells and affects stromal growth, angiogenesis, metastasis or immune surveillance in human glioma.
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