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Published in: Journal of Neuro-Oncology 2/2010

01-11-2010 | Laboratory Investigation - Human/Animal Tissue

IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines

Authors: Qinglin Liu, Gang Li, Ronghui Li, Jie shen, Qiaowei He, Lin Deng, Cai Zhang, Jian Zhang

Published in: Journal of Neuro-Oncology | Issue 2/2010

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Abstract

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.
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Metadata
Title
IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines
Authors
Qinglin Liu
Gang Li
Ronghui Li
Jie shen
Qiaowei He
Lin Deng
Cai Zhang
Jian Zhang
Publication date
01-11-2010
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2010
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-010-0158-0

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