Endostatin and anastellin inhibit distinct aspects of the angiogenic process.
BACKGROUND
Endostatin and anastellin, fragments of collagen type XVIII and fibronectin, respectively, belong to a family of endogenous inhibitors of angiogenesis which inhibit tumor growth and metastasis in a number of mouse models of human cancer. The mechanism of action of these inhibitors is not well understood, but they have great potential usefulness as non-toxic long-term therapy for cancer treatment.


METHODS
In this study, we compare the anti-angiogenic properties of endostatin and anastellin using cell proliferation and transwell migration assays.


RESULTS
Anastellin but not endostatin completely inhibited human dermal microvessel endothelial cell proliferation in response to serum stimulation. Both anastellin and endostatin additively inhibited endothelial cell migration in response to VEGF. Anastellin but not endostatin lowered basal levels of active ERK.


CONCLUSIONS
These data indicate that anastellin and endostatin exert their anti-angiogenic effects by modulating distinct steps in the angiogenic pathway and suggest that matrix-derived inhibitors of angiogenesis may exhibit higher efficacy when used in combination.
Neskey
David M
DM
Center for Cell Biology & Cancer Research, Albany Medical College, Albany, New York 12208, USA. neskyd@mail.amc.edu
Ambesi
Anthony
A
Pumiglia
Kevin M
KM
McKeown-Longo
Paula J
PJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D049109:Cell Proliferation; D043169:Endostatins / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D005353:Fibronectins; D010446:Peptide Fragments; C423921:anastellin