Ivanov Danila, Philippova Maria, Tkachuk Vsevolod, Erne Paul, Resink Thérèse
Cardiovascular Laboratories, Department of Research, Basel University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Exp Cell Res. 2004 Feb 15;293(2):207-18. 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.
T-钙黏蛋白（T-cad）是钙黏蛋白家族中一种特殊的糖基磷脂酰肌醇（GPI）锚定的细胞黏附分子，在心血管系统中广泛表达。T-钙黏蛋白在病变（动脉粥样硬化和再狭窄）血管中的表达谱表明，T-钙黏蛋白的表达与驻留细胞的表型状态之间存在某种关系。我们用人主动脉平滑肌细胞（SMC）和人脐静脉内皮细胞（HUVEC）培养物来研究T-钙黏蛋白可能在调节血管细胞黏附特性中发挥作用这一假说。用重组T-钙黏蛋白蛋白或针对T-钙黏蛋白第一个氨基末端结构域的抗体（抗EC1）包被培养板，可显著降低SMC和HUVEC的黏附与铺展。黏附在T-钙黏蛋白或抗EC1基质上的HUVEC呈现出细长的形态，细胞骨架和黏着斑重新分布到明显的周边位置。这些变化是黏附性较低、具有运动性或促迁移、促血管生成表型的特征。Boyden小室迁移试验表明，T-钙黏蛋白诱导的脱黏附促进细胞向血清梯度迁移。使用腺病毒载体在血管细胞中过表达T-钙黏蛋白本身并不影响细胞黏附或运动性，但会增强T-钙黏蛋白基质诱导的脱离和迁移反应。数据表明，T-钙黏蛋白作为血管细胞的抗黏附信号，从而调节血管细胞表型和迁移特性。
