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


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).


CONCLUSIONS
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.
Mamou
Fatema
F
Department of Radiation Oncology, Comprehensive Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
May
Kerstin S
KS
Schipper
Matthew J
MJ
Gill
Navkiranjit
N
Kariapper
Muhammed S T
MS
Nair
Bindu M
BM
Brewer
George
G
Normolle
Daniel
D
Khan
Mohamed K
MK
D003300:Copper / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D008982:Molybdenum / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate