Abstract
Angiogenesis is involved in tumor growth and metastasis. Endostatin inhibits angiogenesis, but its precise mechanism is not fully understood. To clarify signal transduction involved in endostatin-induced angiogenesis inhibition (endothelial cell growth inhibition), it is important to identify an endostatin receptor, which is the aim of the present study. We hypothesized that vascular endothelial cadherin (VE-cadherin) is an endostatin receptor and found that endostatin induced apoptosis in cultured calf pulmonary artery endothelium (CPAE) cells. Immunoprecipitation and western blots revealed that endostatin specifically bound to VE-cadherin in a Ca2+-dependent manner. Binding of endostatin to VE-cadherin induced tyrosine phosphorylation of VE-cadherin, β-catenin recruitment, and endothelial cell death. Antisense oligonucleotides against VE-cadherin rescued endostatin-induced endothelial cell death. Inhibition of tyrosine phosphorylation of VE-cadherin inhibited endostatin-induced β-catenin recruitment and CPAE cell death. Taken together, we conclude that VE-cadherin is an endostatin receptor.
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- CPAE:
-
calf pulmonary artery endothelium
- PBS:
-
phosphate-buffered saline
- VE:
-
cadherin, vascular endothelial cadherin
- VEGF:
-
vascular endothelial growth factor
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Nemoto, T., Kubota, S. Vascular endothelial cadherin is an endostatin receptor. Biologia 66, 721–726 (2011). https://doi.org/10.2478/s11756-011-0070-x
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DOI: https://doi.org/10.2478/s11756-011-0070-x