Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes

被引:28
作者
Ergün S. [1 ]
Kilic N. [1 ]
Wurmbach J.-H. [1 ,2 ]
Ebrahimnejad A. [3 ]
Fernando M. [1 ]
Sevinc S. [1 ]
Kilic E. [1 ]
Chalajour F. [1 ]
Fiedler W. [4 ]
Lauke H. [1 ]
Lamszus K. [5 ]
Hammerer P. [2 ]
Weil J. [6 ]
Herbst H. [7 ]
Folkman J. [8 ]
机构
[1] Department of Anatomy, University Hospital Eppendorf, Hamburg
[2] Department of Urology, University Hospital Eppendorf, Hamburg
[3] Department of Clinical Chemistry, University Hospital Eppendorf, Hamburg
[4] Department of Hematology/Oncology, University Hospital Eppendorf, Hamburg
[5] Department of Neuropathology, University Hospital Eppendorf, Hamburg
[6] Department of Pharmacology, University Hospital Eppendorf, Hamburg
[7] Department of Pathology, University Hospital Eppendorf, Hamburg
[8] Department of Surgical Research, Children's Hospital, Harvard Medical School, Boston, MA
关键词
Angiogenesis inhibition; Aortic ring assay; Chemotaxis; Collagen XVIII; Endostatin; Endothelial tube assay; HDMEC; Human tumor tissues; Vascular stability;
D O I
10.1023/A:1014027218980
中图分类号
学科分类号
摘要
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.
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页码:193 / 206
页数:13
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