Correlation of thrombospondin-1 and transforming growth factor-β expression with malignancy of glioma
Correlation of thrombospondin-1 and transforming growth factor-β expression with malignancy of glioma
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DOI：
10.1046/j.1440-1789.2000.00327.x
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发表时间：
2000-09-01
期刊：
影响因子：
2.3
通讯作者：
Nukui, H
中科院分区：
文献类型：
--
作者：
Kawataki, T;Naganuma, H;Nukui, H
血小板反应蛋白-1（TSP-1）的表达及其在胶质瘤中的作用尚未得到很好的研究。在本研究中，TSP-1在一组恶性胶质瘤细胞系中的表达以及TSP-1和转化生长因子（TGF-β）蛋白在低度恶性胶质瘤组织中的表达进行了研究。逆转录-聚合酶链反应（RT-PCR）分析显示，9株恶性胶质瘤细胞系中有9株表达TSP-1 mRNA，7株表达TSP-2 mRNA。通过蛋白质印迹分析检测T98 G胶质母细胞瘤细胞系中TSP-1的产生和分泌。上清液中总TSP-1蛋白含量比细胞裂解物中高10倍。通过蛋白质印迹分析检测这些胶质瘤细胞系中TSP-1的分泌。所有胶质瘤细胞系均分泌显著水平的TSP-1。生物测定表明，所有肿瘤细胞系都具有激活潜在TGF-β的能力。TSP-1，TGF-β 1，-β 2，和-β 3的定位进行了化学染色检查手术切除的胶质瘤组织，包括11胶质母细胞瘤，6间变性星形细胞瘤，和8星形细胞瘤。大多数胶质母细胞瘤表达高水平的TSP-1和TGF-β。间变性星形细胞瘤表达中等水平的TSP-1和TGF-β。大多数恶性胶质瘤表达不同水平的TGF-β 1、-β 2和-β 3。然而，这两种蛋白的表达在低级别胶质瘤中较弱。肿瘤周围正常脑组织TSP-1和TGF-β呈阴性或极弱阳性染色。这些结果表明，大多数恶性胶质瘤细胞在体外和体内表达TSP-1，TSP-1和TGF-β在体内的表达与胶质瘤的组织学恶性程度相关。TSP-1和TGF-β的过度表达可能通过在肿瘤组织中产生活性形式的TGF-β而增加恶性胶质瘤的生物学恶性度。
The expression of thrombospondin-1 (TSP-1) and its role in gliomas have not been well examined. In the present study TSP-1 expression in a panel of malignant glioma cell lines and the expression of TSP-1 and transforming growth factor (TGF-beta) proteins in low-grade and malignant glioma tissues were investigated. Reverse transcription-polymerase chain reaction analysis showed that nine of nine malignant glioma cell lines expressed TSP-1 mRNA, and seven of nine glioma lines expressed TSP-2 mRNA. Production and secretion of TSP-1 were examined in the T98G glioblastoma cell line by western blot analysis. Total TSP-1 protein content in the supernatant was 10 times higher than that in the cell lysate. Secretion of TSP-1 was examined in these glioma cell lines by western blot analysis. All glioma lines secreted significant levels of TSP-1. Bioassay showed that all tumor lines had the capacity to activate latent TGF-beta. Localization of TSP-1, TGF-beta1, -beta2, and -beta3 was examined immunohistochemically in surgically resected glioma tissues, including 11 glioblastomas, six anaplastic astrocytomas, and eight astrocytomas. Most glioblastomas expressed high levels of both TSP-1 and TGF-beta. Anaplastic astrocytomas expressed moderate levels of TSP-1 and TGF-beta. Most malignant gliomas expressed various levels of TGF-beta1, -beta2, and -beta3. The expression of both proteins, however, was weak in low-grade gliomas. Normal brain tissues around the tumors were negatively or very weakly positively stained for TSP-1 and TGF-beta. These results indicate that most malignant glioma cells express TSP-1 in vitro and in vivo, and the expression of TSP-1 and TGF-beta in vivo correlates with the histologic malignancy of glioma. Overexpression of both TSP-1 and TGF-beta may increase the biologic malignancy of malignant gliomas, through generating the active form of TGF-beta in tumor tissues.