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.
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- 2.Risau W. Vasculogenesis, angiogenesis and endothelial cell differentiation during embryonic development. In Feinberg RN, Shere GK, Auerbach R (eds): The Development of the Vascular System. Basel: Karger 1991; 58–68.Google Scholar
- 11.Homandberg GA, Williams JE, Grant D et al. Heparin-binding fragments of fibronectin are potent inhibitors of endothelial cell growth. Am J Pathol 1995; 120: 327–32.Google Scholar
- 20.Rehn M, Pihlajaniemi T. Identification of three N-terminal ends of type XVIII collagen chains and tissue-specific differences in the expression of the corresponding transcripts. The longest form contains a novel motif homologous to rat and Drosophila frizzled proteins. J Biol Chem 1995; 270: 4705–11.PubMedCrossRefGoogle Scholar