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Title: Down-regulation of interleukin 6 receptor alpha chain in interleukin 6 transduced melanoma cells causes selective resistance to interleukin 6 but not to oncostatin M. Author: Silvani A, Ferrari G, Paonessa G, Toniatti C, Parmiani G, Colombo MP. Journal: Cancer Res; 1995 May 15; 55(10):2200-5. PubMed ID: 7743524. Abstract: The cytokines interleukin 6 (IL-6) and oncostatin M are able to inhibit the growth of cell lines obtained from early but not advanced melanomas. Resistant cell lines have frequently been found to produce IL-6. Acquisition of IL-6 resistance and the relationship between resistance and endogenous IL-6 production are poorly defined phenomena. We have characterized a panel of melanoma cell lines for susceptibility to IL-6 and oncostatin M and have generated lines that acquired resistance to IL-6 by IL-6 cDNA transduction. These lines retained the previous oncostatin M sensitivity, suggesting that the alpha chain of IL-6 receptor (IL-6R alpha) is involved in the acquisition of resistance. In fact transduced cells lost the ability to bind 125I-IL-6 and to release soluble IL-6R alpha in culture. Moreover, addition of soluble recombinant IL-6R alpha were able to restore IL-6 sensitivity in association with IL-6 production. On the contrary, naturally IL-6 resistant melanoma cell lines were not inhibited by treatment with recombinant soluble IL-6R alpha in association with endogenously produced or recombinant IL-6. These results demonstrate that down-regulation of IL-6 receptor is only one of different mechanisms that are responsible of IL-6 resistance in melanoma cells.[Abstract] [Full Text] [Related] [New Search]