IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1

IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1
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IL-6 通过上调 MMP-2 和 fascin-1 增强 U87MG 人多形性胶质母细胞瘤细胞的侵袭性

DOI:
10.3892/or_00000795
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发表时间:
2010-06-01
期刊:
影响因子:
4.2
通讯作者:
Zhang, Jian
Zhang, Jian
中科院分区:
医学3区
文献类型:
--
作者:
Li, Ronghu;Li, Gang;Zhang, Jian

文献摘要

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多形性胶质母细胞瘤(GBM)复发的主要原因是肿瘤侵犯邻近脑实质。白细胞介素6(IL-6)在胶质瘤恶性进展中的作用尚未明确。在此,我们发现IL-6促进U87 MG人胶质瘤细胞的侵袭,但不促进U343细胞的侵袭。IL-6诱导U87 MG细胞STAT 3活性升高,MMP-2表达和分泌增加。用STAT 3的特异性抑制剂JSI-124或小干扰RNA(siRNA)阻断STAT 3通路可抑制IL-6促进的U87 MG侵袭,同时下调MMP-2。此外,在U87 MG细胞中,IL-6诱导的fascin-1(细胞运动相关蛋白)的快速上调是明显的。然而,这种fascin-1的上调不被JSI-124或siRNA抑制。这些结果表明,STAT 3通路和fascin-1可能在IL-6促进U87 MG细胞的侵袭性中起关键作用。
Invasion into adjacent brain parenchyma is the key cause of recurrent human glioblastoma multiforme (GBM). The role of interleukin 6 (IL-6) in the malignant progression of glioma remains undefined. Here, we found that IL-6 promotes the invasion of U87 MG human glioma cells but not in U343 cells. An advanced level of STAT3 activity, and increased expression and secretion of MMP-2, induced by IL-6 in U87 MG cells were observed. Blocking the STAT3 pathway with specific inhibitors of STAT3, JSI-124 or small interfering RNA (siRNA), inhibited the invasion of U87MG promoted by IL-6 with concomitant down-regulation of MMP-2. Furthermore, rapid up-regulation of fascin-1 (a cell motility-related protein) induced by IL-6 was apparent in U87MG cells. However, this up-regulation of fascin-1 was not inhibited by JSI-124 or siRNA. These results suggest that the STAT3 pathway and fascin-1 may play crucial roles in the invasiveness of U87MG cells promoted by 1L-6.