Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes.
Endostatin decreased vascular endothelial growth factor (VEGF)-induced formation of endothelial tubes and microvessels sprouting from aortic rings and blocked their network. After cessation of treatment, the survival time of endostatin plus VEGF-treated tubes was approximately doubled in comparison to VEGF alone. Endostatin antibody blocked VEGF-induced endothelial tube formation and disrupted existing tubes. Endostatin immunostaining was localized between endothelium and basement membrane and in inter-endothelial junctions of new, but not of quiescent, blood vessels. In tumors grown in SCID mice, endostatin immunostaining was stronger accompanying blood vessel maturation and was significantly prominent in vessels of tumor marginal zone where angiogenesis is highly active. These data indicate a new antiangiogenic action of endostatin stabilizing and maturating endothelial tubes of newly formed blood vessels. Thus, strategies accelerating vascular stabilization and maturation could be promising in tumor therapy.
Ergün
S
S
Department of Anatomy, University Hospital Eppendorf, Hamburg, Germany. erguen@uke.uni-hamburg.de
Kilic
N
N
Wurmbach
J H
JH
Ebrahimnejad
A
A
Fernando
M
M
Sevinc
S
S
Kilic
E
E
Chalajour
F
F
Fiedler
W
W
Lauke
H
H
Lamszus
K
K
Hammerer
P
P
Weil
J
J
Herbst
H
H
Folkman
J
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001013:Aorta, Thoracic; D001485:Basement Membrane / Q000737:chemistry; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009024:Morphogenesis; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D043169:Endostatins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen