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.