The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis.

By D. Brat, A. Bellail, Erwin G. Van Meir. Neuro-Oncology, 2005

752 citations recorded by the source corpus.

Interleukin-8 (IL-8, or CXCL8), which is a chemokine with a defining CXC amino acid motif that was initially characterized for its leukocyte chemotactic activity, is now known to possess tumorigenic and proangiogenic properties as well. In human gliomas, IL-8 is expressed and secreted at high levels both in vitro and in vivo, and recent experiments suggest it is critical to glial tumor neovascularity and progression. Levels of IL-8 correlate with histologic grade in glial neoplasms, and the most malignant form, glioblastoma, shows the highest expression in pseudopalisading cells around necrosis, suggesting that hypoxia/anoxia may stimulate expression. In addition to hypoxia/anoxia stimulation, increased IL-8 in gliomas occurs in response to Fas ligation, death receptor activation, cytosolic Ca(2+), TNF-alpha, IL-1, and other cytokines and various cellular stresses. The IL-8 promoter contains binding sites for the transcription factors NF-kappaB, AP-1, and C-EBP/NF-IL-6, among others. AP-1 has been shown to mediate IL-8 upregulation by anoxia in gliomas. The potential tumor suppressor ING4 was recently shown to be a critical regulator of NF-kappaB-mediated IL-8 transcription and subsequent angiogenesis in gliomas. The IL-8 receptors that could contribute to IL-8-mediated tumorigenic and angiogenic responses include CXCR1 and CXCR2, both of which are G-protein coupled, and the Duffy antigen receptor for cytokines, which has no defined intracellular signaling capabilities. The proangiogenic activity of IL-8 occurs predominantly following binding to CXCR2, but CXCR1 appears to contribute as well through independent, small-GTPase activity. A precise definition of the mechanisms by which IL-8 exerts its proangiogenic functions requires further study for the development of effective IL-8-targeted therapies.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/8389dbbdcfc7bc6b09ba56dddffe839b0b9e25bf

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Citations in the corpus

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development (2013, background): “IL8 is a well-established, hypoxia-responsive factor and has been suggested to have a role in the development of aggressive gliomas (37, 38).”
The role of CXC chemokines and their receptors in cancer. (2008, background): “Like basic fibroblast growth factor (bFGF), it is a strong inducer of angiogenesis [45–47].”
Angiogenesis in brain tumours (2007, background): “grade in glial neoplasms; the most malignant glioma, glioblastoma, shows the highest expression in pseudopalisading cells around areas of necrosis, suggesting that hypoxia/anoxia may stimulate its expressio”
Glioblastoma microvesicles transport RNA and protein that promote tumor growth and provide diagnostic biomarkers (2008, background): “The three angiogenic proteins most enriched were angiogenin, IL-6 and IL-8, all of which have been implicated in glioma angiogenesis and increased malignanc”
Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases (2017, neutral): “The hypoxic and stressed tumor microenvironments stimulate macrophages to secrete CXCL chemokines, a process mediated by NF-κB [24, 243].”