期刊
JOURNAL OF NEURO-ONCOLOGY
卷 109, 期 1, 页码 35-44出版社
SPRINGER
DOI: 10.1007/s11060-012-0875-7
关键词
Glioblastoma; Tumour microenvironment; p38 MAPK inhibitors; Inflammation; Invasion
资金
- Cure for Life Foundation
- Alzheimer's Australia
- JR Wicking Foundation
- JO Wicking Foundation
- National Health and Medical Research Council of Australia [510293, 510294, 1009914]
- University of Sydney [2010-02681]
- Australian Research Council [DP1094232]
- Australian Microscopy and Microanalysis Research Facility (AMMRF) at the University of Sydney
- Australian Research Council [DP1094232] Funding Source: Australian Research Council
Increasing evidence suggests that an inflammatory microenvironment promotes invasion by glioblastoma (GBM) cells. Together with p38 mitogen-activated protein kinase (MAPK) activation being regarded as promoting inflammation, we hypothesized that elevated inflammatory cytokine secretion and p38 MAPK activity contribute to expansion of GBMs. Here we report that IL-1 beta, IL-6, and IL-8 levels and p38 MAPK activity are elevated in human glioblastoma specimens and that p38 MAPK inhibitors attenuate the secretion of pro-inflammatory cytokines by microglia and glioblastoma cells. RNAi knockdown and immunoprecipitation experiments suggest that the p38 alpha MAPK isoform drives inflammation in GBM cells. Importantly, p38 MAPK inhibition strongly reduced invasion of U251 glioblastoma cells in an inflammatory microenvironment, providing evidence for a p38 MAPK-regulated link between inflammation and invasiveness in GBM pathophysiology.
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