Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells.
Recombinant interleukin-24 lacks apoptosis-inducing properties in melanoma cells.
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DOI：
10.1371/journal.pone.0001300
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发表时间：
2007-12-12
期刊：
影响因子：
3.7
通讯作者：
Behrmann I
中科院分区：
文献类型：
--
作者：
Kreis S;Philippidou D;Margue C;Rolvering C;Haan C;Dumoutier L;Renauld JC;Behrmann I
IL-24，也称为黑素瘤分化抗原7（mda-7），是细胞因子的IL-10家族的成员，并且主要由Th 2细胞以及活化的单核细胞产生。IL-24与其两种可能的异二聚体受体IL-20 R1/IL-20 R2和IL-22 R/IL-20 R2中的任何一种结合都会激活靶组织（例如肺、睾丸、卵巢、角质形成细胞和皮肤）中的STAT 3和/或STAT 1。迄今为止，IL-24的生理特性仍然没有得到很好的理解，但现有的数据表明，IL-24通过增加真皮细胞的增殖来影响表皮功能。与其“正常”和生理行为形成鲜明对比的是，IL-24已被报道选择性地和有效地杀死各种癌细胞，特别是黑素瘤细胞，不依赖于受体表达和Jak-STAT信号传导。这些有趣的特性导致了腺病毒表达的IL-24的发展，目前正在临床试验中进行评估。使用三种不同的方法，我们分析了一个大的黑色素瘤细胞系的IL-24和IL-24受体的表达，发现没有一个研究的细胞系表达足够量的功能性受体对，因此没有反应IL-24刺激与Jak/STAT激活。三种细胞系的结果与先前的研究形成对比，先前的研究报道了IL-24受体的存在和IL-24刺激后STAT 3的活化。此外，评价四种不同来源和模式的IL-24给药（商业重组IL-24、细菌表达的GST-IL-24融合蛋白、由转染的Hek细胞产生的IL-24、瞬时过表达的IL-24），与适当的对照处理相比，未检测到细胞死亡的诱导或增加。因此，我们得出结论，细胞因子IL-24本身在黑色素瘤细胞中没有癌症特异性肿瘤诱导特性。
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 Th2 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.
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