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Journal of Neuro-Oncology

, Volume 101, Issue 2, pp 227–235 | Cite as

IL-8 is a mediator of NF-κB induced invasion by gliomas

  • Baisakhi Raychaudhuri
  • Michael A. Vogelbaum
Laboratory Investigation - Human/Animal Tissue

Abstract

Glioblastoma (GBM) is the most common and deadly form of primary brain tumor with a median survival of eleven months, despite use of extensive chemotherapy, radiotherapy and surgery. We have previously shown that nuclear factor-kappa B (NF-κB) is aberrantly expressed in GBM tumors and primary cell lines derived from tumor tissue. Here we show that IL-8, a chemokine is also aberrantly expressed by GBM cell lines and expression of IL-8 is in large part, attributable to the aberrant activation of NF-κB. We hypothesized that invasiveness of GBM cells is driven at least in part by aberrantly expressed IL-8. In support of the hypothesis we found that treatment of glioma cells with an IL-8 neutralizing antibody markedly decreased their invasiveness compared to cells treated with control IgG or left untreated. Furthermore, downregulation of IL-8 protein production with use of IL-8 targeted siRNA also resulted in decreased invasion in matrigel. We next investigated the presence of IL-8 receptors by FACS analysis and found that GBM cells (U87, U251, D54 and LN229) only express CXCR1 but not CXCR2. Treatment of U87 cells with a blocking CXCR1 antibody reduced their invasion through matrigel. Finally, we found that addition of exogenous IL-8, following downregulation of NF-κB which results in loss of endogenous IL-8 production, incompletely restored tumor cell invasion. Our data indicate that IL-8 is necessary but not solely responsible for glioma cell invasion and mediates its effect in an autocrine manner.

Keywords

IL-8 NF-κB CXCR1 invasion glioma 

Supplementary material

11060_2010_261_MOESM1_ESM.pdf (32 kb)
Supplementary material 2 (PDF 32 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  1. 1.Brain Tumor and Neuro-Oncology Center, Neurological InstituteCleveland ClinicClevelandUSA

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