T-cadherin suppresses angiogenesis in vivo by inhibiting migration of endothelial cells

• Published in: Angiogenesis (London) 2007-09, Vol.10 (3), p.183-195
• Main Authors: Rubina, Kseniya, Kalinina, Natalia, Potekhina, Alexandra, Efimenko, Anastasia, Semina, Ekaterina, Poliakov, Alexei, Wilkinson, David G, Parfyonova, Yelena, Tkachuk, Vsevolod
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Apoptosis; Arteriosclerosis; Atherosclerosis; Biomarkers - metabolism; Blood vessels; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cadherins - pharmacology; Cadherins - physiology; Capillary tubes; Cell Line; Cell migration; Cell Movement - drug effects; Cell proliferation; Cells, Cultured; Collagen - metabolism; Culture Media, Conditioned - pharmacology; Drug Combinations; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - physiology; Endothelium, Vascular - cytology; Fluorescent Antibody Technique, Direct; Glycosylphosphatidylinositol; Humans; In vivo methods and tests; Kidney - cytology; L Cells; Laminin - metabolism; Mice; Mice, Nude; Models, Biological; Neoplasm Transplantation; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Proliferating Cell Nuclear Antigen - metabolism; Proteoglycans - metabolism; Restenosis; Stroma; T-cadherin; Transplantation, Homologous; Umbilical Veins - cytology; Vascular proliferative disorders; Vascularization
• ISSN: 0969-6970; 1573-7209
• DOI: 10.1007/s10456-007-9072-2

Our previous studies have revealed the abundant expression of T-cadherin--a glycosylphosphatidylinositol (GPI)-anchored member of cadherin superfamily--in endothelial and mural cells in the heart and vasculature. The upregulation of T-cadherin in vascular proliferative disorders such as atherosclerosis and restenosis suggests the involvement of T-cadherin in vascular growth and remodeling. However, the functional significance of this molecule in the vasculature remains unknown. The effect of T-cadherin on angiogenesis in vivo was evaluated using Matrigel implant model. We demonstrate that T-cadherin overexpression in L929 cells injected in Matrigel inhibits neovascularization of the plug. In vitro T-cadherin inhibits the directional migration of endothelial cells, capillary growth, and tube formation but has no effect on endothelial cell proliferation, adhesion, or apoptosis in vitro. These data suggest that T-cadherin expressed in the stroma could act as a negative guidance cue for the ingrowing blood vessels and thus could have an important potential therapeutic application.