Interleukin-2 enhances the growth of human melanoma cells derived from primary but not from metastatic tumours

Previously, we demonstrated that in vitro treatment of B16F10 murine melano ma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. T o further investigate the role played by IL-2 in human melanomas, we studie d the expression of IL-2/IL-2 receptor and the effect of IL-2 on the prolif eration of melanoma cell lines derived from primary (A375 and RMS cell line s) and metastatic (Hs294T cell line) tumours, We found a constitutive expre ssion of cytoplasmic IL-2 and alpha, beta and gamma -subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in th e culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells, Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, partic ularly in A375 and RMS cells, in which an inhibition of the proliferation r ate was observed when IL-2 was blocked. Moreover, the combination of anti-I L-2R beta and anti-IL-2R gamma blocking antibodies induced a significant do wn-regulation of cell proliferation in the three melanoma cell lines, and t he combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma bl ocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs 294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 en dogenously produced by melanoma cells. These data show that IL-2 mag modula te the growth of melanoma cells through autocrine or/and paracrine mechanis ms.