Angiogenesis

, Volume 4, Issue 3, pp 193–206 | Cite as

Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes

  • Süleyman Ergün
  • Nerbil Kilic
  • Jan-Henner Wurmbach
  • Alireza Ebrahimnejad
  • Malkanthi Fernando
  • Sema Sevinc
  • Ergin Kilic
  • Fariba Chalajour
  • Walter Fiedler
  • Heidrun Lauke
  • Katrin Lamszus
  • Peter Hammerer
  • Joachim Weil
  • Hermann Herbst
  • Judah Folkman

Abstract

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.

aortic ring assay angiogenesis inhibition chemotaxis collagen XVIII endostatin endothelial tube assay HDMEC human tumor tissues vascular stability 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Süleyman Ergün
    • 1
  • Nerbil Kilic
    • 1
  • Jan-Henner Wurmbach
    • 1
    • 2
  • Alireza Ebrahimnejad
    • 3
  • Malkanthi Fernando
    • 1
  • Sema Sevinc
    • 1
  • Ergin Kilic
    • 1
  • Fariba Chalajour
    • 1
  • Walter Fiedler
    • 4
  • Heidrun Lauke
    • 1
  • Katrin Lamszus
    • 5
  • Peter Hammerer
    • 2
  • Joachim Weil
    • 6
  • Hermann Herbst
    • 7
  • Judah Folkman
    • 8
  1. 1.Department of AnatomyUniversity Hospital EppendorfHamburgGermany
  2. 2.Department of UrologyUniversity Hospital EppendorfHamburgGermany
  3. 3.Department of Clinical ChemistryUniversity Hospital EppendorfHamburgGermany
  4. 4.Department of Hematology/OncologyUniversity Hospital EppendorfHamburgGermany
  5. 5.Department of NeuropathologyUniversity Hospital EppendorfHamburgGermany
  6. 6.Department of PharmacologyUniversity Hospital EppendorfHamburgGermany
  7. 7.Department of PathologyUniversity Hospital EppendorfHamburgGermany
  8. 8.Department of Surgical Research, Children's HospitalHarvard Medical SchoolBostonUSA

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