ANTAGONISTIC REGULATION OF CELL-MIGRATION BY EPIDERMAL GROWTH-FACTOR AND GLUCOCORTICOID IN HUMAN GASTRIC-CARCINOMA CELLS

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 d etermined by a wound assay. However, these actions of EGF were inhibit ed if the cells were pretreated with dexamethasone, a synthetic glucoc orticoid. Dexamethasone increased cell adhesion to collagen type IV an d laminin, but not to poly-L-lysine and fibronectin. In contrast, EGF did not affect cell adhesion to these extracellular matrices whether d examethasone was present or not. Dexamethasone enhanced the protein le vels of both alpha 1 and beta 1 integrin subunits, and that of the alp ha 1 beta 1 heterodimer. Further, flow cytometric analysis revealed th at dexamethasone increased the expression of beta 1 and alpha 1 integr in subunits at the cell surface, whereas EGF increased expression of b eta 1 and alpha 2 subunits at the cell surface. Antibodies against alp ha 1 and beta 1 integrin subunits inhibited the increased cell adhesio n seen in the presence of dexamethasone. An immunofluorescence study i ndicated 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 thi s EGF-induced preferential formation was not observed if the cells wer e pretreated with dexamethasone. These results Suggest that glucocorti coid increased cell adhesion to the extracellular matrix via alpha 1 b eta 1 integrin, and thereby antagonized EGF-induced cell migration. (C ) 1998 Wiley-Liss, Inc.