Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells.
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.
Kreis
Stephanie
S
Laboratoire de Biologie et Physiologie Intégrée, Life Science Research Unit, University of Luxembourg, Luxembourg. stephanie.kreis@uni.lu <stephanie.kreis@uni.lu>
Philippidou
Demetra
D
Margue
Christiane
C
Rolvering
Catherine
C
Haan
Claude
C
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Behrmann
Iris
I
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D000099180:Interleukin-24
D017931:DNA Primers; D007378:Interleukins; D011994:Recombinant Proteins; D014157:Transcription Factors; D000099180:Interleukin-24