Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells.

Abstract

IL-24, also known as melanoma differentiation antigen 7 (mda-7), is a member of the IL-10 family of cytokines and is mainly produced by Th(2) cells as well as by activated monocytes. Binding of IL-24 to either of its two possible heterodimeric receptors IL-20R1/IL-20R2 and IL-22R/IL-20R2 activates STAT3 and/or STAT1 in target tissues such as lung, testis, ovary, keratinocytes and skin. To date, the physiological properties of IL-24 are still not well understood but available data suggest that IL-24 affects epidermal functions by increasing proliferation of dermal cells. In stark contrast to its "normal" and physiological behaviour, IL-24 has been reported to selectively and efficiently kill a vast variety of cancer cells, especially melanoma cells, independent of receptor expression and Jak-STAT signalling. These intriguing properties have led to the development of adenovirally-expressed IL-24, which is currently being evaluated in clinical trials. Using three different methods, we have analysed a large panel of melanoma cell lines with respect to IL-24 and IL-24 receptor expression and found that none of the investigated cell lines expressed sufficient amounts of functional receptor pairs and therefore did not react to IL-24 stimulation with Jak/STAT activation. Results for three cell lines contrasted with previous studies, which reported presence of IL-24 receptors and activation of STAT3 following IL-24 stimulation. Furthermore, evaluating four different sources and modes of IL-24 administration (commercial recombinant IL-24, bacterially expressed GST-IL-24 fusion protein, IL-24 produced from transfected Hek cells, transiently over-expressed IL-24) no induction or increase in cell death was detected when compared to appropriate control treatments. Thus, we conclude that the cytokine IL-24 itself has no cancer-specific apoptosis-inducing properties in melanoma cells.

• Authors: Stephanie Kreis, Demetra Philippidou, Christiane Margue, Catherine Rolvering, Claude Haan, Laure Dumoutier, Jean-Christophe Renauld, Iris Behrmann
• Journal: PloS one (PLoS One) Vol. 2 Issue 12 Pg. e1300 (Dec 12 2007) ISSN: 1932-6203 [Electronic] United States
• PMID: 18074024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Interleukins
• Recombinant Proteins
• Transcription Factors
• interleukin-24

Topics

• Apoptosis (physiology)
• Base Sequence
• Blotting, Western
• Cell Line
• Cell Proliferation (drug effects)
• DNA Primers
• Gene Expression Profiling
• Humans
• Interleukins (physiology)
• Melanoma (genetics, pathology)
• Recombinant Proteins (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors (metabolism)