Co-Investigator(Kenkyū-buntansha) |
SHIBAMOTO Sayumi SETSUNAN UNIVERSITY,FACUTY OF PHARMACEUTICAL SCIENCES,RESEARCH ASSOCIATE, 薬学部, 助手 (80178920)
HORI Takamitsu SETSUNAN UNIVERSITY,FACUTY OF PHARMACEUTICAL SCIENCES,ASSISTANT PROFESSOR, 薬学部, 講師 (00199522)
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Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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Research Abstract |
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
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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
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