Association of morphological differentiation with enhanced surface antigen expression and susceptibility to natural killer cell lysis in theophylline-treated human melanoma cells.

Human and animal melanomas undergo maturation spontaneously in vivo and in vitro, and as a result of experimental manipulation in vitro. To gain a better understanding of this phenomenon, we studied the effects of theophylline on a cultured human malignant melanoma cell line (CaCL 73-36). We observed a dose-dependent inhibition of cell growth with a reduction in plating efficiency of 16, 64, and 99% at concentrations of theophylline of 0.1, 1.0, and 2.0 mM, respectively. Theophylline-treated cells showed morphological changes consistent with a more differentiated state such as increased dendrite formation and contact inhibition. Expression of surface HLA-A,B,C antigens and beta-2-microglobulin was enhanced 15- and fivefold, respectively. Finally, cells treated with theophylline for 96 h showed a five- to eightfold increase in sensitivity to lysis by natural killer cells. These findings have obvious bearing on the potential use of theophylline in the treatment of malignant melanoma.