IL-8 is a mediator of NF-κB induced invasion by gliomas
IL-8 is a mediator of NF-κB induced invasion by gliomas
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DOI：
10.1007/s11060-010-0261-2
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发表时间：
2011-01-01
影响因子：
3.9
通讯作者：
Vogelbaum, Michael A.
中科院分区：
文献类型：
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作者：
Raychaudhuri, Baisakhi;Vogelbaum, Michael A.
胶质母细胞瘤（GBM）是最常见和致命的原发性脑肿瘤，尽管使用广泛的化疗，放疗和手术，中位生存期为11个月。我们先前已经证明核因子-κ B（NF-κ B）在GBM肿瘤和肿瘤组织来源的原代细胞系中异常表达。在这里，我们表明，IL-8，一种趋化因子，也异常表达的GBM细胞系和IL-8的表达是在很大程度上，归因于NF-κ B的异常激活。我们假设GBM细胞的侵袭性至少部分由异常表达的IL-8驱动。为了支持这一假设，我们发现，与用对照IgG处理或不处理的细胞相比，用IL-8中和抗体处理胶质瘤细胞显著降低了它们的侵袭性。此外，使用IL-8靶向siRNA下调IL-8蛋白产生也导致基质胶中的侵袭降低。我们接下来通过FACS分析研究了IL-8受体的存在，发现GBM细胞（U87、U251、D54和LN 229）仅表达CXCR 1而不表达CXCR 2。用阻断CXCR 1抗体处理U87细胞减少了它们通过基质胶的侵袭。最后，我们发现，在NF-κ B下调导致内源性IL-8产生丧失后，加入外源性IL-8不能完全恢复肿瘤细胞侵袭。我们的数据表明，IL-8是必要的，但不是唯一负责胶质瘤细胞的侵袭，并介导其自分泌方式的影响。
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-kappa B) 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-kappa B. 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-kappa B 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.