Refractoriness to antivascular endothelial growth factor treatment: role of myeloid cells.
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.
Shojaei
Farbod
F
Genentech, Inc., South San Francisco, California 94080, USA.
Ferrara
Napoleone
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D039481:CD11b Antigen / Q000096:biosynthesis; D005768:Gastrointestinal Hormones / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009479:Neuropeptides / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D039481:CD11b Antigen; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor