| Abstract: | Epidermal growth factor (EGF) induced the disruption and scattering of colonies of TMK-1, a cell line derived from a human gastric carcinoma. A stimulatory action of EGF on cell migration was also observed as determined by a wound assay. However, these actions of EGF were inhibited if the cells were pretreated with dexamethasone, a synthetic glucocorticoid. Dexamethasone increased cell adhesion to collagen type IV 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 not. Dexamethasone enhanced the protein levels of both α1 and β1 integrin subunits, and that of the α1 β1 heterodimer. Further, flow cytometric analysis revealed that dexamethasone increased the expression of β1 and α1 integrin subunits at the cell surface, whereas EGF increased expression of β1 and α2 subunits at the cell surface. Antibodies against α1 and β1 integrin subunits inhibited the increased cell adhesion seen in the presence of dexamethasone. An immunofluorescence study indicated that dexamethasone increased the formation of focal adhesions along the entire edges of cell colonies. In contrast, EGF led to the formation of focal adhesions preferentially at the cell front, and this EGF-induced preferential formation was not observed if the cells were pretreated with dexamethasone. These results suggest that glucocorticoid increased cell adhesion to the extracellular matrix via α1 β1 integrin, and therebyantagonized EGF-induced cell migration. J. Cell. Physiol. 176:127–137, 1998. © 1998 Wiley-Liss, Inc. |
