The goal of these studies is to evaluate the modulation of the transformed cell phenotype by dexamethasone and evaluate functional peptide domains of fibronectin (FN). Studies have shown that there is a 10-fold induction of FN by dexamethasone, which is associated with an increase in cell spreading and adhesion. FN production in normal cells also was induced by dexamethasone. The dexamethasone induction is blocked by the glucocorticoid antagonist RU-486; however, the basal rate of FN production was not altered by RU-486. These studies have relied on pulse chase experiments and immunoprecipitation and radioimmunoassay. To further elucidate the possible mechanisms, future studies will look at cell hybrids or fusions of nucleus and cytoplasm from responding and nonresponding cells to ascertain the regulation of this phenomenon. Hybridoma studies have been performed, and additional ones will continue to be evaluated to delineate functional regions of the FN molecule. Heparin-binding regions of the FN molecule have been isolated and are observed to have an isoelectric point of 9.5. It has been observed that FN and fragments of FN will promote the chemotaxis of human and animal tumor cells in vitro in a form of chemotaxis. Monoclonal antibodies are being used to isolate a peptide fragment of FN that will promote the migration of tumor cells. It is hoped that this may shed some light on one component of metastasis, namely, the directed migration of tumor cells. The generation and characterization of additional monoclonal antibodies to FN will potentially permit us to define regions of the molecule that have important functions in the movement and, therefore, metastasis of tumor cells. Further studies will evaluate the regulation of FN production of dexamethasone in normal and transformed cells. We will attempt to use molecular biology to probe the hormonal or genetic control of FN production. (A)
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