Endostatin Inhibits the Vascular Endothelial Growth Factor-Induced Mobilization of Endothelial Progenitor Cells

Gunter Schuch, John V. Heymach, Masashi Nomi, Marcelle Machluf, Jeremy Force, Anthony Atala, Joseph P. Eder, Judah Folkman, Shay Soker

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Circulating endothelial cells (CECs) are present in peripheral blood and have been shown to contribute to normal and pathological neovascularization. Antiangiogenic molecules can inhibit neovascularization in tumors and other sites, but their effect on CECs has not yet been determined. We hypothesize that angiogenic factors will increase the number of CECs, and conversely, antiangiogenic treatment will reduce these numbers. Mice treated with high levels of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1-positive cells in peripheral blood and endothelial cell colonies compared with vehicle-treated controls. These changes were accompanied by increased bone marrow neovascularization. In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and reduced bone marrow vascularization. Endostatin-induced apoptosis was probably responsible for the decreased number of CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the VEGF-induced increase in CECs. These results were further confirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of β-galactosidase-expressing peripheral blood mononuclear cells. We propose that endothelial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs can serve as a surrogate marker for the biological activity of antiangiogenic treatment.

Original languageEnglish
Pages (from-to)8345-8350
Number of pages6
JournalCancer Research
Volume63
Issue number23
StatePublished - Dec 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schuch, G., Heymach, J. V., Nomi, M., Machluf, M., Force, J., Atala, A., Eder, J. P., Folkman, J., & Soker, S. (2003). Endostatin Inhibits the Vascular Endothelial Growth Factor-Induced Mobilization of Endothelial Progenitor Cells. Cancer Research, 63(23), 8345-8350.