Induced interleukin-8 expression in gliomas by tumor-associated macrophages

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• 作者：Tse-Ming Hong ; Lee-Jene Teng ; Chia-Tung Shun ; Mei-Chen Peng and Jui-Chang Tsai
• 关键词：Angiogenic factor ; Cytokine ; Glioma ; IL ; 8 ; Macrophages ; NF ; κ ; B
• 刊名：Journal of Neuro-Oncology
• 出版年：2009
• 出版时间：July, 2009
• 年：2009
• 卷：93
• 期：3
• 页码：289-301
• 全文大小：662.7 KB

文摘

The tumor microenvironment affects tumor initiation, progression, and metastasis. However, it is still not clear how stromal cells interact with the tumor cells. By using a cytokine array immunoblot assay, we showed that interleukin (IL)-8, IL-6, and RANTES (regulated upon activation normal T-cell expressed and secreted) proteins were up-regulated in GBM8401 glioma cells after coculture with human THP-1-derived macrophages. IL-8 is a chemokine with leukocyte chemotactic, tumorigenic, and proangiogenic properties. To evaluate the correlation of IL-8 expression with tumor-associated macrophages and angiogenesis, 43 glioma specimens were studied. The results showed that the IL-8 mRNA expression and microvessel count in glioma surgical specimens correlated positively with the density of tumor-associated macrophages. We further showed that IL-8 mRNA expression in GBM8401 cells increased dramatically, by 28–210-fold, after being cocultured with macrophages. This increase could also be induced by macrophage-conditioned medium, tumor necrosis factor-α, IL-1α, and IL-1β, and could be suppressed by anti-inflammatory agents including pyrrolidine dithiocarbamate, pentoxifylline, or dexamethasone. These findings imply that macrophage infiltration may be the common feature shared by cancer and inflammation, and macrophages could play a role in promoting glioma growth and angiogenesis by inducing IL-8 expression in glioma cells via inflammatory stimuli or the nuclear factor kappa B pathway.