Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens
✍ Scribed by Olga Kholmanskikh; Nicolas van Baren; Francis Brasseur; Sabrina Ottaviani; Julie Vanacker; Nathalie Arts; Pierre van der Bruggen; Pierre Coulie; Etienne De Plaen
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 869 KB
- Volume
- 127
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
We report that melanoma cell lines expressing the interleukin‐1 receptor exhibit 4‐ to 10‐fold lower levels of mRNA of microphthalmia‐associated transcription factor (MITF‐M) when treated with interleukin‐1β. This effect is NF‐κB and JNK‐dependent. MITF‐M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL‐1β reduced by 40–100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL‐1α or IL‐1β secreted by two melanoma cell lines that did not express MITF‐M, suggesting an autocrine MITF‐M downregulation. We estimate that ∼13% of melanoma cell lines are MITF‐M‐negative and secrete IL‐1 cytokines. These results indicate that the repression of melanocyte‐differentiation genes by IL‐1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.