Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment.

The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-alpha-induced apoptosis.

Wagley Y, Yoo YC, Seo HG, Rhee MH, Kim TH, Kang KW, Nah SY, Oh JW

Department of Anatomy, College of Medicine, Chosun University, 375 Seosuk-Dong, Dong-Gu, Gwangju, Republic of Korea.

Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-alpha in combination with IFN-gamma in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-alpha-resistant B16/F10.9 melanoma cells. A low dose of TNF-alpha or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-alpha-resistant F10.9 melanoma cells to TNF-alpha-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-alpha resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-alpha responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-alpha-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-alpha-resistant melanoma cells to TNF-alpha-induced apoptosis, may provide a new target for immunotherapy.

Published 13 February 2007 in Biochem Biophys Res Commun, 354(4): 985-91.
Full-text of this article is available online (may require subscription).

© 2004-2008 Melanoma Research Today. All Rights Reserved.