Adenosine-3′,5′-Cyclic Monophosphate Levels and Adenosine-3′,5′-Cyclic Monophosphate Phosphodiesterase Activity in Metastasizing and Nonmetastasizing Rat Mammary Carcinomas 2

Abstract

The adenosine-3′,5′-cyclic monophosphate phosphodiesterase (cPDE) activity in the homogenates of 6 spontaneously metastasizing, nonimmunogenic, glycocalyx- shedding rat mammary carcinomas (MT) was assayed and compared with four histologically and growth rate-matched nonmetastasizing, immunogenic MT. The levels of this enzyme were 2.5 times higher in the nonmetastasizing tumors. To rule out the possibility of the presence of inhibitor(s) or stimulator(s) of cPDE, homogenates from a non metastasizing and from a widely metastasizing tumor were mixed. cPDE from both non metastasizing and metastasizing MT showed two apparent K_m and two corresponding V_max. The activity of the enzyme at concentrations of 1 ,µM (low K_m) and 100 ,µM (high K_m) adenosine-3′,5′ -cyclic monophosphate (cAMP) decreased in parallel with increasing metastasizing capacity. About 50% of the low and the high K_m cPDE was in the cytosol in both groups, whereas the rest was particulate. The proportion of low and high K_m activity was similar in all the fractions except in the plasma membrane of the metastasizing tumors where the percent of low K_m enzyme was three times higher than that of the high Km. The steady-state levels of cAMP were 1.3–2.0 times higher in the metastasizing tumors, inversely proportional to their cPDE activities.