M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes.
The impact of the immune response in malignancy is poorly understood. While immune cells can destroy transformed cells, the targeting and accumulation of monocytes and macrophages at tumor sites may promote tumor metastases. The growth factor M-CSF is important in promoting monocyte survival. Since M-CSF(-/-) mice are protected against tumor metastases, we hypothesized that M-CSF induced monocytes to produce angiogenic factors that facilitate metastases. In this study we demonstrate that recombinant human M-CSF induces freshly isolated normal human monocytes to produce and release the growth factor vascular endothelial growth factor (VEGF) in a dose-dependent manner, which peaked at 5 days in culture. VEGF released by these monocytes is biologically active, as cell-free supernatants from these M-CSF-stimulated monocytes induced tube formation in HUVEC. Network formation by these HUVECs after treatment with supernatants from monocytes stimulated with M-CSF were inhibited by anti-VEGF, but not by the isogenic control, Abs. Collectively, these data support an important role for M-CSF and monocytes in VEGF production and angiogenesis.
Eubank
Tim D
TD
Dorothy M. Davis Heart and Lung Research Institute, Ohio State University, 473 West 12th Avenue, Columbus, OH 43210, USA.
Galloway
Michelle
M
Montague
Christine M
CM
Waldman
W James
WJ
Marsh
Clay B
CB
D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D002460:Cell Line; D002474:Cell-Free System / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007797:Laminin; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000276:immunology / Q000502:physiology*; D019899:Paracrine Communication / Q000502:physiology; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007106:Immune Sera; D007797:Laminin; D011509:Proteoglycans; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D016173:Macrophage Colony-Stimulating Factor; D003094:Collagen