Antagonistic regulation of cell migration by epidermal growth factor and glucocorticoid.

细胞迁移是免疫系统中形态发生、组织修复、炎症反应和相互作用的关键事件。已知多种生长因子如表皮生长因子(EGF)可刺激细胞迁移。事实上，我们发现表皮生长因子刺激人胃癌细胞系TMK-L的细胞迁移。在这项研究中，我们已经报道，如果细胞被地塞米松(一种合成的糖皮质激素)预处理，EGF诱导的细胞迁移被抑制。由于细胞与多种细胞外基质如胶原、纤维连接蛋白和层粘连蛋白的相互作用被认为是细胞迁移的关键，我们研究了糖皮质激素和EGF对TMK-1细胞与细胞外基质黏附的影响。地塞米松可增加细胞与V型胶原和层粘连蛋白的粘附性，但不能增加细胞与多聚L赖氨酸和纤维连接蛋白的粘附性。相反，无论是否存在地塞米松或n…，表皮生长因子都不影响细胞与这些细胞外基质的黏附。细胞-细胞外基质的相互作用是由一组整合蛋白介导的，每个整合蛋白都是由一个非共价的阿尔法亚基和一个贝塔亚基组成的细胞表面蛋白。然后，我们检测了经地塞米松或EGF处理的TMK-1细胞中各种α和β亚基的表达水平，地塞米松提高了α1和β1整合素亚单位以及α1β1异二聚体的蛋白水平。此外，流式细胞仪分析显示，地塞米松增加了细胞表面α1和β1亚单位的表达，而EGF则增加了细胞表面α2和β1亚单位的表达。针对α1和β1整合素亚单位的抗体可抑制地塞米松引起的细胞黏附增加。这些结果表明，糖皮质激素通过α1β1整合素增加细胞与细胞外基质的黏附，从而拮抗EGF诱导的细胞迁移。较少

Cell migration is a critical event in morphogenesis, tissue repair inflammatory reactions, and interactions in the immune system. A variety of growth factors such as epidermal growth factor (EGF) have been known to stimulate cell migration. In fact, we found that EGF stimulated cell migration of TMK-l, a cell line derived from a human gastric carcinoma. In this study, we have reported that the EGF-induced cell migration was inhibited if the cells were pretreated with dexamethasone, a synthetic glucocorticoid. Since interaction of cells with a variety of extracellular matrices such as collagen, fibronectin, and laminin is thought to be crucial for cell migration, we studied the effect of glucocorticoid and EGF on cell adhesion of TMK-1 to extracellular matrices. Dexamethasone increased cell adhesion to collagen typelV and laminin, but not to poly-L-lysine and fibronectin. In contrast, EGF did not affect cell adhesion to these extracellular matrices whether dexamethasone was present or n … More ot.Cell-extracellular matrix interactions are mediated by a family of integriris, each of which is a cell-surface protein consisting of an alpha subunit noncovalently associated with a beta subunit. We then examined the expression level of a variety of alpha and beta subunits in TMK-1 cells which had been pretreated with dexamethasone or EGF.Dexamethasone enhanced the protein levels of both alpha 1 and beta 1 integrin subunits, and that of the alpha1beta 1 heterodimer. Further, flow cytometric analysis revealed that dexamethasone increased the expression of alpha 1and beta 1 subunits at the cell surface, whereas EGF increased expression of alpha 2 and beta 1 subunits at the cell surface. Antibodies against alpha 1 and beta 1 integrin subunits inhibited the increased cell adhesion seen in the presence of dexamethasone. These results suggest that glucocorticoid increased cell adhesion to the extracellular matrix via alpha 1beta1 integrin, and thereby antagonized EGF-induced cell migration. Less