Journal of Neuro-Oncology

, Volume 100, Issue 2, pp 165–176 | Cite as

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

  • Qinglin Liu
  • Gang Li
  • Ronghui Li
  • Jie shen
  • Qiaowei He
  • Lin Deng
  • Cai Zhang
  • Jian Zhang
Laboratory Investigation - Human/Animal Tissue

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.

Keywords

IL-6 Glioblastoma Invasion Migration Angiogenesis Fascin-1 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Qinglin Liu
    • 1
  • Gang Li
    • 1
  • Ronghui Li
    • 1
  • Jie shen
    • 1
  • Qiaowei He
    • 1
  • Lin Deng
    • 1
  • Cai Zhang
    • 2
  • Jian Zhang
    • 2
  1. 1.Department of Neurosurgery, Qi Lu HospitalShandong UniversityJinanPeople’s Republic of China
  2. 2.Institute of Immunopharmacology and ImmunotherapySchool of Pharmaceutical Sciences, Shandong UniversityJinanPeople’s Republic of China

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