Phorbol myristate acetate (PMA) suppresses polarization and locomotion and alters F-actin content of Walker carcinosarcoma cells.

This study demonstrates a novel feature of PMA, its ability to suppress chemokinetic polarization and locomotion of tumor cells. Walker carcinosarcoma cells exhibit two distinct types of polarization and locomotion, i.e. spontaneous polarization characterized by ruffles at the front and stimulated polarization and locomotion in response to the microtubule-disassembling agents colchicine, vinblastine and nocodazole, which are characterized by blebbing at the front. The tumor promotor phorbol myristate acetate (PMA), but not phorbol, was found to suppress both types of polarization and random locomotion at concentrations between 10(-8) and 10(-6)M. The effect of 10(-6)M PMA was virtually complete within 5 min. Inhibition of locomotion was due to both a reduction in the speed of migrating cells and the proportion of migrating cells. Changes in shape and chemokinesis of Walker carcinosarcoma cells were associated with alterations in the relative amount and the topographical distribution of F-actin as determined by NBD-phallacidin binding. Suppression by PMA was associated with loss of the polar topographical distribution of F-actin visualized by NBD-phallacidin binding. In the presence of PMA, the relative amount of F-actin was higher than in unstimulated controls and lower in cells exposed to microtubule-disassembling agents.