Some effects of the tumor promoter 12-0-tetradecanoylphorbol 13-acetate on cell interactions in vitro

Studies were made of the effects of the potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA), 4-O-methyl TPA (4-O-MeTPA), and 4 alpha phorbol 12,13-didecanoate (4 alpha PDD) on the aggregation of embryonic chick cells in gyratory shaker culture, a model system useful for the study of cell adhesion and cell interactions. TPA and, to a lesser extent, 4-O-MeTPA significantly reduced the neural retina aggregate size at concentrations as low as 10(-9) M and 10(-8) M, respectively. An inactive isomer, 4 alpha PDD, had no effect up to 10(-6) M. The reduction in aggregate size appeared related to promoter activity since dexamethasone, a steroid that inhibits tumor promotion by TPA, significantly reversed the inhibitory effect of TPA. None of the agents tested affected the sorting pattern in mixed neural retina and heart cultures. The results indicate that intercellular adhesion, as determined by extent of aggregation, is reduced in the presence of TPA. This inhibition is considered to be related to the tumor-promoting activity of TPA.