1. Tetrathiomolybdate blocks bFGF- but not VEGF-induced incipient angiogenesis in vitro.
- Author
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Mamou F, May KS, Schipper MJ, Gill N, Kariapper MS, Nair BM, Brewer G, Normolle D, and Khan MK
- Subjects
- Copper metabolism, Endothelial Cells cytology, Endothelial Cells metabolism, Fibroblast Growth Factor 2 pharmacology, Humans, Neovascularization, Physiologic physiology, Vascular Endothelial Growth Factor A pharmacology, Endothelial Cells drug effects, Fibroblast Growth Factor 2 antagonists & inhibitors, Molybdenum pharmacology, Neovascularization, Physiologic drug effects, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Background: Angiogenesis is a multi-step process which involves endothelial cell sprouting from existing blood vessels, followed by migration, proliferation, alignment and tube formation. Tetrathiomolybdate (TM) is a multi-hit antiangiogenic agent with actions against multiple angiogenic pathways. These inhibitory effects of TM are attributed to its potent copper level-reducing property. Copper is needed for activation of various angiogenic pathways at the transcriptional and protein levels., Materials and Methods: The direct effects of TM on angiogenesis of endothelial cells were examined using an in vitro sprout-forming system., Results: It was shown that depletion of copper by TM selectively repressed bFGF-induced, but not VEGF-induced sprout formation (an early angiogenic step)., Conclusion: This model permitted the separation of VEGF- and bFGF- induced early angiogenesis in vitro, and indicated the existence of mechanistic differences between bFGF- and VEGF- induced early angiogenic events.
- Published
- 2006