Atypical GPI-anchored T-cadherin stimulates angiogenesis in vitro and in vivo

Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2222-30. doi: 10.1161/01.ATV.0000238356.20565.92. Epub 2006 Jul 27.


Objective: T-cadherin (T-cad) is an atypical GPI-anchored member of the cadherin superfamily. In vascular tissue, T-cad expression is increased during atherosclerosis, restenosis, and tumor neovascularization. In vitro, overexpression and/or homophilic ligation of T-cad on endothelial cells (ECs) facilitates migration, proliferation, and survival. This study investigated T-cad effects on angiogenesis.

Methods and results: In vitro, T-cad homophilic ligation induced arrangement of ECs into a capillary-like network in a 2-dimensional model of EC differentiation and stimulated in-gel endothelial sprout outgrowth in an EC spheroid model and a modified Nicosia tissue assay. Sprouting from spheroids composed of adenoviral-infected T-cad overexpressing ECs or T-cad siRNA transfected ECs were significantly increased or reduced, respectively. In vivo, T-cad potentiated VEGF effects on neovascularization in a model of myoblast-mediated gene transfer to mouse skeletal muscle; vessel caliber after co-delivery of T-cad and VEGF was significantly greater than after delivery of VEGF alone.

Conclusions: We unequivocally identify T-cad as a novel modulator of angiogenesis and suggest that this molecule can be exploited as a target for modulation of therapeutic angiogenesis, as well as for prevention of pathological conditions associated with abnormal neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents* / pharmacology
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cadherins / pharmacology
  • Cadherins / physiology*
  • Cell Differentiation / physiology
  • Cell Line
  • Drug Synergism
  • Endothelial Cells / cytology
  • Endothelial Cells / physiology
  • Endothelium, Vascular / growth & development
  • Gene Transfer Techniques
  • Glycosylphosphatidylinositols / physiology*
  • Humans
  • Mice
  • Muscle, Skeletal / blood supply
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Spheroids, Cellular
  • Transfection
  • Vascular Endothelial Growth Factor A / pharmacology


  • Angiogenesis Inducing Agents
  • Cadherins
  • Glycosylphosphatidylinositols
  • H-cadherin
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A