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

  • Laboratory Investigation - Human/Animal Tissue
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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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Acknowledgments

This project was supported by the National Natural Science Foundation of China (No. 30872645). We thank Aijun Hao and Shidou Zhao from the Department of Histology and Embryology of Shandong University for their kind assistance.

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Authors and Affiliations

  1. Department of Neurosurgery, Qi Lu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Qinglin Liu, Gang Li, Ronghui Li, Jie shen, Qiaowei He & Lin Deng

  2. Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Cai Zhang & Jian Zhang

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  1. Qinglin Liu
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  2. Gang Li
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Correspondence to Gang Li.

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Liu, Q., Li, G., Li, R. et al. IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol 100, 165–176 (2010). https://doi.org/10.1007/s11060-010-0158-0

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