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

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 melanom...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-03, Vol.354 (4)
Main Authors: Wagley, Yadav, Yoo, Yung-Choon, Seo, Han Geuk, Rhee, Man Hee, Kim, Tae-Hyoung, Kang, Keon Wook, Nah, Seung-Yeol, Oh, Jae-Wook
Format: Article
Language:English
Subjects:
ANTIBODIES
APOPTOSIS
BORON CHLORIDES
IMMUNOTHERAPY
MELANOMAS
PEPTIDES
RADIOLOGY AND NUCLEAR MEDICINE
RECEPTORS
STIMULATION
TOXICITY
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.01.083