Cell adhesion molecule T-cadherin regulates vascular cell adhesion, phenotype and motility

• Published in: Experimental cell research 2004-02, Vol.293 (2), p.207-218
• Main Authors: Ivanov, Danila, Philippova, Maria, Tkachuk, Vsevolod, Erne, Paul, Resink, Thérèse
• Format: Article
• Language: English
• Subjects: Antibodies - pharmacology; Cadherins - genetics; Cadherins - metabolism; Cell adhesion; Cell Adhesion - physiology; Cell Line; Cell Movement - physiology; Cell Size - physiology; Cytoskeleton - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Focal Adhesions - metabolism; Gene Expression - physiology; Humans; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Phenotype; Protein Structure, Tertiary - physiology; Signal Transduction - physiology; T-cadherin
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2003.09.030

T-cadherin (T-cad), an unusual glycosylphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion molecules, is widely expressed in the cardiovascular system. The expression profile of T-cad within diseased (atherosclerotic and restenotic) vessels indicates some relationship between expression of T-cad and the phenotypic status of resident cells. Using cultures of human aortic smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC) we investigate the hypothesis that T-cad may function in modulating adhesive properties of vascular cells. Coating of culture plates with recombinant T-cad protein or with antibody against the first amino-terminal domain of T-cad (anti-EC1) significantly decreased adhesion and spreading of SMC and HUVEC. HUVECs adherent on T-cad or anti-EC1 substratum exhibited an elongated morphology and associated redistribution of the cytoskeleton and focal adhesions to a distinctly peripheral location. These changes are characteristic of the less-adhesive, motile or pro-migratory, pro-angiogenic phenotype. Boyden chamber migration assay demonstrated that the deadhesion induced by T-cad facilitates cell migration towards a serum gradient. Overexpression of T-cad in vascular cells using adenoviral vectors does not influence cell adhesion or motility per se, but increases the detachment and migratory responses induced by T-cad substratum. The data suggest that T-cad acts as an anti-adhesive signal for vascular cells, thus modulating vascular cell phenotype and migration properties.