The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis
TLDR
A precise definition of the mechanisms by which IL-8 exerts its proangiogenic functions requires further study for the development of effectiveIL-8-targeted therapies.Abstract:
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 Ca2+, TNF-α, IL-1, and other cytokines and various cellular stresses. The IL-8 promoter contains binding sites for the transcription factors NF-κB, 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-κB-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.read more
Citations
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Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog,T. Wurdinger,van Rijn S,Dimphna H. Meijer,Gainche L,Miguel Sena-Esteves,William T. Curry,Bob S. Carter,Anna M. Krichevsky,Xandra O. Breakefield +9 more
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
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Angiogenesis in brain tumours
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TL;DR: Emerging preclinical and clinical data indicate that anti-VEGF therapies are potentially effective in glioblastoma and can transiently normalize tumour vessels, creating a window of opportunity for optimally combining chemotherapeutics and radiation.
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Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development
Paulina Kucharzewska,Helena C. Christianson,Johanna E. Welch,Katrin J. Svensson,Erik Fredlund,Markus Ringnér,Matthias Mörgelin,Erika Bourseau-Guilmain,Johan Bengzon,Mattias Belting +9 more
TL;DR: It is shown that the proteome and mRNA profiles of exosome vesicles closely reflect the oxygenation status of donor glioma cells and patient tumors, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.
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The role of CXC chemokines and their receptors in cancer
TL;DR: The role of CXC chemokines and their receptors in tumorigenesis, including angiogenesis, attraction of leukocytes to tumor sites and induction of tumor cell migration and homing in metastatic sites is discussed.
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