Cyclic AMP phosphodiesterase inhibitors depress production of plasminogen activator by Chinese hamster ovary cells.

Oncogenic transformation in a limited number of cell systems has been shown by others to be associated with an increased production of extracellular proteolytic activators that convert the plasma proenzyme, plasminogen, to the active protease, plasmin. In the present study, two cyclic AMP phosphodiesterase inhibitors (theophylline, papaverine) markedly depressed the production of intracellular and extracellular plasminogen activator by Chinese hamster ovary cells of the CHO-Kl line in serum-free medium. Prostaglandin E₁ had a moderately similar effect on the production of only extracellular plasminogen activator. The ability to control experimentally the level of production of plasminogen activator should be of value in elucidating the possible biological role of the proteolytic action of plasmin on the surface of CHO cells, and the cell surface alterations which accompany oncogenic transformation.