Abstract
CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. Recently, we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to angiogenic blockade by vascular endothelial growth factor (VEGF) antibodies. This effect was traced to a pathway of CD11b+Gr1+-mediated angiogenesis that is, at least in part, driven by the secreted protein Bv8, which is up-regulated by the important myeloid growth factor granulocyte colony-stimulating factor (G-CSF). Thus, G-CSF may promote tumor angiogenesis through a Bv8-dependent pathway that bypasses VEGF and renders tumors refractory to anti-VEGF therapy.
MeSH terms
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Angiogenesis Inhibitors / pharmacology
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Animals
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Antigens, Neoplasm / chemistry
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CD11b Antigen / biosynthesis
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Gastrointestinal Hormones / biosynthesis
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Gene Expression Regulation, Neoplastic*
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Granulocyte Colony-Stimulating Factor / metabolism
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Humans
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Models, Biological
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Myeloid Cells / cytology*
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Myeloid Cells / metabolism
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Neovascularization, Pathologic*
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Neuropeptides / biosynthesis
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Vascular Endothelial Growth Factor A / antagonists & inhibitors*
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Vascular Endothelial Growth Factor A / metabolism*
Substances
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Angiogenesis Inhibitors
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Antigens, Neoplasm
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CD11b Antigen
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Gastrointestinal Hormones
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Neuropeptides
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PROK2 protein, human
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Vascular Endothelial Growth Factor A
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Granulocyte Colony-Stimulating Factor