Selection and characterization of a variant of human melanoma cell line, A375 resistant to growth inhibitory effects of oncostatin M (OM): coresistant to interleukin 6 (IL-6).

Human melanoma cell line A375 is extremely sensitive to growth inhibitory effects of oncostatin M (OM). A375 cells resistant to the antiproliferative effect of OM were isolated by exposing OM-sensitive cells to ethyl methane sulfonate (EMS) for 24 h followed by continuous exposure to OM. An A375 subline resistant to OM-induced growth inhibition was selected by a limiting dilution technique and designated 4-1.10". The resistant cells were completely refractory to OM even up to a concentration of 500 ng/ml. Interestingly, the resistant cells were also nonresponsive to the growth inhibitory effects of interleukin-6 (IL-6). Other cytokines such as transforming growth factor beta (TGF-beta), interleukin-1 (IL-1), and tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) exhibited similar growth inhibitory effects on OM-sensitive or -resistant cells. OM-resistant cells were found to possess approximately 20% of OM receptors with the same affinities as compared to the parental OM-sensitive cells. However, the affinities and number of receptors for IL-6 were the same on both cell types. The OM treatment did not alter the cyclic AMP (cAMP) level of either the parental or the resistant cells. The OM-resistant cell line will be very useful in elucidating the mechanism of OM-elicited growth inhibition.