Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 51
Analysis of interleukin-24-induced signalling in melanoma cells
Stephanie Kreis*, Georg A. Munz**, Laure Dumoutier***, Claude Haan*, Waraporn
Komyod**, Jean-Christophe Renauld***, Peter C. Heinrich** and Iris Behrmann*
*Laboratoire de Biologie et Physiologie Integrée, Université du Luxembourg, 162a,
avenue de la Faïencerie, L-1511 Luxemburg, ** Dept. of Biochemistry, RWTH Aachen
Medical School, D-52074 Aachen, Germany, ***Ludwig Institute for Cancer Research,
University Catholique de Louvain, B-1200 Brussels, Belgium
Interleukin (IL)-24, which was initially named “melanoma differentiation-associated gene 7”
(mda-7), is an IL-10-type cytokine that has been discovered by means of differentiation
therapy and subtraction hybridization in melanoma cells. Via two receptor complexes (IL-
20R1/IL-20R2 and IL-22R/IL-20R2), IL-24 can activate tyrosine kinases of the Janus family
(Jaks) and STAT transcription factors in target cells. In addition to this „classical“ signalling
pathway, IL-24 has the unique property to induce apoptosis in many different cancer cells, but
not in normal cells, when applied via an adenoviral vector or as GST fusion protein.
Moreover, it promotes anti-oncogenic bystander activity, it inhibits angiogenesis, synergises
with radiation, and modulates immune responses. However, the mechanisms of cancer cell
selectivity as well as the receptor-independent signalling events leading to IL-24-induced
apoptosis remain unclear.
A panel of 20 melanoma cell lines as well as normal human keratinocytes and primary human
melanocytes were analysed with respect to their Jak-STAT signalling capacity in response to
IL-24 stimulation. Although all cells are RT-PCR-positive for expression of specific cytokine
receptor subunits, only keratinocytes responded to IL-24 stimulation by phosphorylation of
STAT3. Neither the primary melanocytes nor the 20 tested melanoma lines reacted to IL-24
stimulation. Of note, we did not observe STAT3 phosphorylation in
unstimulated melanoma cells.
To further investigate the cancer apoptosis-inducing function of IL-24, we have generated and
expressed a GST-IL-24 fusion protein and variants thereof, based on differential splicing and
on a structure/function comparison of IL-10 like cytokines. Furthermore, inducible stable
melanoma cell lines expressing IL-24 are being generated and first resulting data will be
discussed.
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