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J Neurooncol. 2009 Jul;93(3):289-301. doi: 10.1007/s11060-008-9786-z. Epub 2009 Jan 21.

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

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  • 1NTU Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.


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 2(8)-2(10)-fold, after being cocultured with macrophages. This increase could also be induced by macrophage-conditioned medium, tumor necrosis factor-alpha, IL-1alpha, and IL-1beta, 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.

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