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Endothelial Cell Tube Formation Assay for the In Vitro Study of Angiogenesis
08:12

Endothelial Cell Tube Formation Assay for the In Vitro Study of Angiogenesis

Published on: September 1, 2014

Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin

T L Moser1, D J Kenan, T A Ashley

  • 1Department of Pathology and Duke University School of Nursing, Duke University Medical Center, Durham, NC 27710, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 7, 2001
PubMed

Insights

Angiostatin inhibits tumor angiogenesis by blocking endothelial cell ATP metabolism. This occurs via surface-bound ATP synthase, suggesting a novel mechanism for anti-angiogenic therapies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Angiostatin is known to inhibit tumor angiogenesis by affecting endothelial cell migration and proliferation.
  • The precise mechanism of angiostatin action is not fully understood.
  • F(1)-F(O) ATP synthase has been identified as a potential angiostatin-binding site on endothelial cells.

Purpose of the Study:

  • To investigate the presence and function of F(1) ATP synthase on the endothelial cell surface.
  • To determine if angiostatin affects the activity of surface-associated ATP synthase.
  • To explore the role of endothelial ATP metabolism in angiostatin's anti-angiogenic effects.

Main Methods:

  • Demonstration of F(1) ATP synthase components on endothelial cell surfaces using immunofluorescence.
  • Assessing ATP synthesis activity of surface-bound enzyme via dual-label TLC and bioluminescence assays.
  • Evaluating the effect of angiostatin and anti-ATP synthase antibodies on enzyme activity in cell-based and biochemical assays.

Main Results:

  • All catalytic core components of F(1) ATP synthase are present and functional on the endothelial cell surface, forming discrete structures.
  • Angiostatin inhibits both ATP synthase and ATPase activities of the surface-bound enzyme.
  • Antibodies against ATP synthase subunits mimic angiostatin's endothelial cell-inhibitory effects.

Conclusions:

  • Angiostatin suppresses tumor vascularization by inhibiting endothelial cell surface ATP metabolism.
  • Surface-associated ATP synthase activity is a key target for angiostatin's anti-angiogenic action.
  • Antibodies targeting ATP synthase subunits can act as angiostatin mimetics, offering potential therapeutic strategies.

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