Tetrathiomolybdate blocks bFGF- but not VEGF-induced incipient angiogenesis in vitro

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.

The direct effects of TM on angiogenesis of endothelial cells were examined using an in vitro sprout-forming system.

It was shown that depletion of copper by TM selectively repressed bFGF-induced, but not VEGF-induced sprout formation (an early angiogenic step).

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.