Dexamethasone regulation of plasminogen activator in embryonic and tumor-derived human cells.

Abstract

Plasminogen activator (PA) activity in human polymorphonuclear leukocytes and embryonic lung cell cultures is reduced substantially following treatment with glucocorticoids such as dexamethasone. To determine whether tumor-derived cells responded similarly, we compared the effect of dexamethasone on the PA activity of a variety of tumor-derived and embryonic cell cultures. These cultures produced either exclusively M.W. 55,000 to 60,000 urokinase-like PA, exclusively M.W. 73,000 anti-urokinase immunoglobulin-resistant PA, or a mixture of both types of enzyme. Treatment of embryonic human lung, kidney, and uveal melanocyte cell cultures with 10-7 m dexamethasone strongly inhibited both extracellular and cell-associated PA activity. One lung adenocarcinoma-derived and two renal carcinoma-derived cell cultures also showed substantial inhibition of PA activity under these conditions. In contrast, treatment of six independently isolated, melanoma-derived cultures with 10-7 m dexamethasone produced no detectable inhibition of either extracellular or cell-associated PA activity. All six melanoma-derived cultures produced exclusively or principally the M.W. 73,000-type PA. [3H]Dexamethasone-binding assays indicated that the content and size of the cytoplasmic dexamethasone-binding protein were similar in both melanoma-derived and embryonic lung cultures. Our in vitro results suggest that, in vivo , physiological concentrations of glucocorticoids will inhibit the PA activity expressed by many embryonic and several tumor-derived cell types but not that expressed by the melanoma-derived cells.