Induced interleukin-8 expression in gliomas by tumor-associated macrophages.
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.
Hong
Tse-Ming
TM
NTU Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
Teng
Lee-Jene
LJ
Shun
Chia-Tung
CT
Peng
Mei-Chen
MC
Tsai
Jui-Chang
JC
D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000276:immunology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger