IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines
IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines
复制标题
IL-6促进U251和T98G细胞系中胶质母细胞瘤细胞侵袭和血管生成
DOI：
10.1007/s11060-010-0158-0
复制
发表时间：
2010-11-01
影响因子：
3.9
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Liu, Qinglin;Li, Gang;Zhang, Jian
白细胞介素-6（IL-6）是人胶质母细胞瘤细胞中的生长和存活因子，在恶性进展中起重要作用。然而，它在胶质母细胞瘤侵袭中的作用仍然未知。这项研究显示了IL-6如何促进U251和T98 G胶质母细胞瘤细胞系的细胞侵袭和迁移。其机制包括蛋白酶依赖性和非依赖性两种。用IL-6刺激增加两种细胞系中MMP 9的表达，但对MMP 2的表达没有影响。Fascin-1是一种细胞骨架结合蛋白，在细胞迁移和侵袭中起关键作用。其结合方式直接影响细胞形态和变形倾向。IL-6暴露后，fascin-1表达以IL-6剂量依赖性方式增加。免疫荧光还显示，在IL-6暴露后，fascin-1的结合方式发生了变化，导致细胞更具侵袭性的表型。三个最常强调的侵袭相关信号通路，包括JAK-STAT 3，p42/44 MAPK和PI 3 K/AKT，被验证以进一步阐明其潜在的机制。只有STAT 3丝氨酸727位点的磷酸化抑制IL-6的刺激作用，而JAK-STAT 3通路阻断剂JSI-124则抑制IL-6的侵袭和迁移促进作用，表明JAK/STAT 3通路介导信号转导。此外，IL-6还以旁分泌方式促进血管内皮细胞迁移，从而促进肿瘤血管生成和侵袭。这些结果表明，IL-6促进胶质母细胞瘤细胞的侵袭和血管生成，并可能是一个潜在的抗侵袭的目标。
Interleukin-6 (IL-6) is a growth and survival factor in human glioblastoma cells and plays an important role in malignant progression. However, its role in glioblastoma invasion is still unknown. This study shows how IL-6 promotes cell invasion and migration in U251 and T98G glioblastoma cell lines. The underlying mechanism includes both protease-dependent and -independent manners. Stimulation with IL-6 increased MMP9 expression in the two cell lines but had no influence on MMP2 expression. Fascin-1 is a cell skeleton binding protein and plays a key role in cell migration and invasion. Its binding style directly influences cell morphology and tendency to become deformed. After IL-6 exposure, fascin-1 expression increased in an IL-6 dose-dependent manner. Immunofluorescence also revealed that the binding style of fascin-1 had changed after IL-6 exposure, resulting in a more invasive phenotype of the cells. Three most commonly emphasized invasion-associated signaling pathways, including JAK-STAT3, p42/44 MAPK, and PI3K/AKT, were verified to further illustrate its underlying mechanism. Only phosphorylation of STAT3 at ser 727 site paralleled the IL-6 stimulation, and JSI-124, a specific JAK-STAT3 pathway blocker, deterred the invasion and migration promotive effect of IL-6, indicating that the JAK/STAT3 pathway mediates signal transduction. Furthermore, IL-6 also acts in a paracrine fashion to promote vascular endothelial cell migration, thus facilitating tumor angiogenesis and invasion. These results suggest that IL-6 promotes glioblastoma cell invasion and angiogenesis and may be a potential anti-invasion target.