Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, PR China.
Oncol Rep. 2010 Jun;23(6):1553-9. doi: 10.3892/or_00000795.
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 IL-6.
侵犯邻近脑实质是人类多形性胶质母细胞瘤（GBM）复发的关键原因。白细胞介素 6（IL-6）在神经胶质瘤恶性进展中的作用仍未确定。在这里，我们发现 IL-6 促进 U87 MG 人神经胶质瘤细胞的侵袭，但不促进 U343 细胞的侵袭。在 U87 MG 细胞中，IL-6 诱导 STAT3 活性的高级水平、MMP-2 的表达和分泌增加。用 STAT3 的特异性抑制剂 JSI-124 或小干扰 RNA（siRNA）阻断 STAT3 途径，可抑制 IL-6 促进的 U87MG 细胞的侵袭，并伴随 MMP-2 的下调。此外，IL-6 可迅速诱导 U87MG 细胞中 fascin-1（一种与细胞运动相关的蛋白）的上调。然而，JSI-124 或 siRNA 不能抑制 fascin-1 的这种上调。这些结果表明，STAT3 途径和 fascin-1 可能在 IL-6 促进 U87MG 细胞侵袭中起关键作用。
