Article: article from journal or magazin.
Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis.
The Journal of Experimental Medicine
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8-binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8-binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2.
Anaerobiosis, Antigens, CD/biosynthesis, Blotting, Northern, Cell Hypoxia/immunology, Chemotaxis, Leukocyte, Disease Progression, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, In Situ Hybridization, Interleukin-8/biosynthesis, Interleukin-8/genetics, Necrosis, Neovascularization, Physiologic/immunology, RNA, Messenger/biosynthesis, Receptors, Interleukin/biosynthesis, Receptors, Interleukin-8A, Spheroids, Cellular, Up-Regulation
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