T-cadherin suppresses angiogenesis in vivo by inhibiting migration of endothelial cells.
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.
Rubina
Kseniya
K
Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, 31-5, Lomonosovsky av., Moscow, 119192, Russia. rksenia@cardio.ru
Kalinina
Natalia
N
Potekhina
Alexandra
A
Efimenko
Anastasia
A
Semina
Ekaterina
E
Poliakov
Alexei
A
Wilkinson
David G
DG
Parfyonova
Yelena
Y
Tkachuk
Vsevolod
V
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007668:Kidney / Q000166:cytology; D007739:L Cells; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D014184:Transplantation, Homologous; D014471:Umbilical Veins / Q000166:cytology
D015415:Biomarkers; D015820:Cadherins; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen