TGF-β1 promotes motility and invasiveness of glioma cells through activation of ADAM17.

TGF-β1 promotes motility and invasiveness of glioma cells through activation of ADAM17.
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DOI:
10.3892/or.2011.1195
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发表时间:
2011-05
期刊:
影响因子:
4.2
通讯作者:
Chopp M
Chopp M
中科院分区:
医学3区
文献类型:
--
作者:
Lu Y;Jiang F;Zheng X;Katakowski M;Buller B;To SS;Chopp M

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转化生长因子β 1(TGF-β1)属于结构相关的多肽因子家族。TGF-β在恶性胶质瘤侵袭的病理生物学中起重要作用。本研究旨在探讨肿瘤坏死因子-α转换酶(TACE/ADAM 17)信号通路对TGF-β1刺激的T98 G胶质瘤细胞迁移和侵袭过程的影响。我们发现TGF-β1增加胶质瘤细胞的迁移和侵袭能力。加入TGF-β1受体抑制剂SB 431542可降低TGF-β1刺激的胶质瘤细胞的迁移和侵袭能力。此外,暴露于ADAM 17抑制剂TAPI-2也可阻断TGF-β1诱导的迁移和侵袭。TGF-β1可上调ADAM 17 mRNA和蛋白表达。SB 431542和TAPI-2可阻断TGF-β1诱导的ADAM 17蛋白表达。总之,这些结果表明TGF-β1通过刺激ADAM 17促进胶质瘤细胞的细胞迁移和侵袭。
The transforming growth factor beta1 (TGF-β1) belongs to a family of structurally related polypeptide factors. TGF-beta plays an important role in the pathobiology of invasion of malignant gliomas. The objective of the present study is to investigate the impact of TNF-α converting enzyme (TACE/ADAM17) signalling on the process of TGF-β1-stimulated migration and invasion of T98G glioma cells. We found that TGF-β1 increased migration and invasiveness in glioma cells. Addition of the TGF-β1 receptor inhibitor, SB431542, reduced the TGF-β1-stimulated migration and invasiveness of glioma cells. In addition, TGF-β1-induced migration and invasiveness were also blocked by exposure to an ADAM17 inhibitor, TAPI-2. Furthermore, ADAM17 mRNA and protein expression were up-regulated by TGF-β1. Treatment with SB431542 and TAPI-2 blocked TGF-β1-induced ADAM17 protein expression. In summary, these results indicate that TGF-β1 promotes cell migration and invasiveness of glioma cells through stimulation of ADAM17.
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