Dexamethasone-induced adhesion in hepatoma cells: the role of plasminogen activator

Abstract

TRANSFORMED CELLS are frequently less adhesive than normal cells. This decrease in adhesion has been associated with the loss of specific cell surface proteins, changes in morphology, alterations in the underlying cytoskeleton and the increased activity of the serine protease, plasminogen activator^1–3. Hepatoma tissue culture (HTC) cells exhibit increased levels of adhesion to glass^4,5 and decreased plasminogen activator activity^6,7 when incubated in the presence of the synthetic glucocorticoid, dexamethasone. Plasminogen activator converts plasminogen in serum to plasmin. It has been shown that plasmin causes the reversible dissociation of intracellular actin-containing cables in anchorage-dependent rat embryo cells⁸ and may also be partially responsible for decreased adhesion of Rous sarcoma virus-transformed chicken embryo fibroblasts³. Cell–substrate adhesion presumably requires specific cell surface glycoproteins and intact cytoskeletal elements^9,10. It is possible that plasmin acts either to modify ‘adhesive’ proteins on the cell surface or to disrupt linkages between these surface components and the underlying cytoskeleton. We have used variant HTC cells selectively resistant to the dexamethasone inhibition of plasminogen activator⁶ to test the hypothesis that hormonal induction of cell adhesion is secondary to the inhibition of plasminogen activator which in turn allows the accumulation of the glycoproteins necessary for adhesion. We have modified cell adhesion assay techniques^5,11 to provide a sensitive measure of cell–substrate adhesion for both wild-type and variant HTC cells in the presence and absence of serum and plasminogen. We report here that plasminogen activator does not have an important role in the hormonal regulation of HTC cell adhesiveness.