Inhibitory effect of full-length human endostatin on in vitro angiogenesis.
Endostatin, a C-terminal product of collagen XVIII, is a very powerful angiogenesis inhibitor. In vivo experiments in mice indicate that endostatin dramatically reduces tumor mass without causing the onset of any resistance to the treatment. Recently, a 12-aa shorter human endostatin has been purified from plasma, but is ineffective in in vitro angiogenesis assays. Here we report that the full-length human recombinant endostatin has a potent inhibitory activity in in vitro angiogenesis assays. Two powerful angiogenic factors were used to stimulate endothelial cells: FGF-2 and VEGF-165. Endostatin prevented cell growth both in the basal condition and after stimulation with FGF-2 or VEGF-165. Migration of microvascular endothelial cells toward FGF-2 or VEGF-165 was impaired, both when cells were pretreated with the inhibitor and when endostatin was added together with the growth factors. Furthermore, experiments of inhibition of proliferation performed on nonmicroendothelial cells showed that endostatin was ineffective. This study indicates that human endostatin is a potent angiogenesis inhibitor and suggests its use in human anticancer therapy.
Taddei
L
L
Department of Biochemical Sciences, Viale GB Morgagni 50, Florence, 50134, Italy.
Chiarugi
P
P
Brogelli
L
L
Cirri
P
P
Magnelli
L
L
Raugei
G
G
Ziche
M
M
Granger
H J
HJ
Chiarugi
V
V
Ramponi
G
G
D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics / Q000494:pharmacology*; D043170:Collagen Type XVIII; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014699:Venules / Q000166:cytology / Q000187:drug effects
D043170:Collagen Type XVIII; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen