Down-regulation of interleukin 6 receptor α chain in interleukin 6 transduced melanoma cells causes selective resistance to interleukin 6 but not to oncostatin M

A. Silvani, G. Ferrari, G. Paonessa, C. Toniatti, G. Parmiani, M. P. Colombo

Research output: Contribution to journalArticle

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 α chain of IL-6 receptor (IL-6Rα) is involved in the acquisition of resistance. In fact transduced cells lost the ability to bind 125I-IL-6 and to release soluble IL-6Rα in culture. Moreover, addition of soluble recombinant IL-6Rα 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-6Rα 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.

Original languageEnglish
Pages (from-to)2200-2205
Number of pages6
JournalCancer Research
Volume55
Issue number10
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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