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 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 alpha1 and beta1 integrin subunits, and that of the alpha1 beta1 heterodimer. Further, flow cytometric analysis revealed that dexamethasone increased the expression of beta1 and alpha1 integrin subunits at the cell surface, whereas EGF increased expression of beta1 and alpha2 subunits at the cell surface. Antibodies against alpha1 and beta1 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 alpha1 beta1 integrin, and thereby antagonized EGF-induced cell migration.
Murakami
N
N
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Fukuchi
S
S
Takeuchi
K
K
Hori
T
T
Shibamoto
S
S
Ito
F
F
D015820:Cadherins / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000737:chemistry; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D019000:Phosphotyrosine / Q000032:analysis; D013274:Stomach Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D016023:Integrins; D007797:Laminin; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D003094:Collagen