Relationship of IL-19 to the Metastatic Potential of a Lung Tumor

J. Rothenberg, Marlow B. Hernandez, N. Bray, T. Weaver, Russell Zhuravsky
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引用次数: 1

Abstract

Interleukin 19 (IL-19), an anti-inflammatory and immunosuppressant cytokine, has been shown to affect the function and viability of lung fibroblasts, and has been implicated in lung cancer metastasis. 1-4 The purpose of this research was to compare gene expression profiles of IL-19 genes (through the collection of RNA isolates) between two lines of mice, an original tumor line (DA-3/TM), and a surgically resected metastatic tumor line (DA-3/TM-Mets). A battery of laboratory procedures were used to study metastasis of cancer from a primary tumor cell line, DA-3/TM, and from a metastatic site, DA-3/TM-Mets. Metastatic lesions in animal models were isolated, cultured, and analyzed in order to observe the changes between the primary and metastatic line. Both PCR and then Western Blots were performed to verify the initial findings from the metastatic lesions of mice. It was found that DA-3/TM-Mets, had more nodule metastasis throughout the lungs of BALB/c mice compared to that of DA-3/TM. A gene array performed showed that the key difference was IL-19, which was 30X higher in DA-3/TM-Mets than in DA-3/TM. This suggests a significant difference at the gene level. However, it is important to develop a new model to look at these tumor cell lines at the protein level in order to observe if this difference holds true. The data acquired shows promising results. Higher concentrations of IL-19 in the DA-3/ TMMets line may lead to the conclusion that IL-19 is exhibiting immunosuppressive activity, which does not allow the BALB/c mice’s immune system to fight off a tumor, resulting in their death. Therefore, there appears to be a direct correlation between the metastasis of cancer and the protein IL-19’s immunosuppressive effects.
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IL-19与肺肿瘤转移潜能的关系
白细胞介素19 (IL-19)是一种抗炎和免疫抑制的细胞因子,已被证明可以影响肺成纤维细胞的功能和活力,并与肺癌转移有关。1-4本研究的目的是比较两种小鼠系,原始肿瘤系(DA-3/TM)和手术切除的转移性肿瘤系(DA-3/TM- mets)之间IL-19基因的基因表达谱(通过收集RNA分离物)。我们使用了一系列实验室程序来研究原发肿瘤细胞系DA-3/TM和转移部位DA-3/TM- mets的癌症转移。对动物模型中的转移灶进行分离、培养和分析,观察原发系和转移系之间的变化。采用PCR和Western Blots验证小鼠转移灶的初步发现。结果发现,与DA-3/TM相比,DA-3/TM在BALB/c小鼠中有更多的肺结节转移。基因阵列分析显示,关键差异是IL-19,在DA-3/TM- mets中IL-19比DA-3/TM高30倍。这表明在基因水平上存在显著差异。然而,重要的是开发一种新的模型,在蛋白质水平上观察这些肿瘤细胞系,以观察这种差异是否成立。所获得的数据显示出可喜的结果。DA-3/ TMMets细胞系中较高浓度的IL-19可能导致IL-19表现出免疫抑制活性,这使得BALB/c小鼠的免疫系统无法抵抗肿瘤,从而导致其死亡。因此,肿瘤的转移与IL-19蛋白的免疫抑制作用有直接关系。
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