IL-6 is required for glioma development in a mouse model
IL-6 is required for glioma development in a mouse model
复制标题
DOI：
10.1038/sj.onc.1207455
复制
发表时间：
2004-04-22
期刊：
影响因子：
8
通讯作者：
Weis, J
中科院分区：
文献类型：
--
作者：
Weissenberger, J;Loeffler, S;Weis, J
多效性细胞因子白介素-6 （IL-6）参与多种癌症的恶性进展和细胞凋亡抵抗。尽管IL-6在恶性胶质瘤中升高，且胶质瘤细胞对IL-6有反应，但其在胶质瘤形成中的功能作用尚不清楚。我们通过将胶质纤维酸性蛋白（GFAP）病毒src致癌基因转基因小鼠与IL-6缺失小鼠杂交，研究了IL-6在小鼠自发性星形细胞瘤模型中的作用。我们在这里表明，消融IL-6可以阻止这些易感动物的肿瘤形成，但不影响肿瘤前星形胶质细胞增生。此外，我们发现转录因子信号转导和转录激活因子（STAT） 3的磷酸化和核易位，这是IL-6信号传导的先决条件，在51例WHO II-IV级人类胶质瘤和所有实验小鼠肿瘤中被研究。再加上STAT3激活随着恶性肿瘤的增加而增加，这些发现表明IL-6在星形细胞瘤的发生和恶性进展中起着重要作用。
The pleiotropic cytokine interleukin- 6 (IL-6) contributes to malignant progression and apoptosis resistance of various cancer types. Although IL-6 is elevated in malignant gliomas, and glioma cells respond to IL-6, its functional role in gliomagenesis is unclear. We have investigated this role of IL-6 in a mouse model of spontaneous astrocytoma by crossbreeding glial fibrillary acidic protein (GFAP)-viral src oncogene transgenic mice with IL-6-deficient mice. We show here that ablation of IL-6 prevents tumour formation in these predisposed animals, but did not affect preneoplastic astrogliosis. Moreover, we demonstrate phosphorylation and nuclear translocation of the transcription factor signal transducer and activator of transcription (STAT) 3, a prerequisite for IL-6 signalling, in 51 human gliomas WHO grade II-IV and all experimental mouse tumours investigated. Together with the observation that STAT3 activation increases with malignancy, these findings indicate an important role for IL-6 in the development and malignant progression of astrocytomas.