Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China.
Aging (Albany NY). 2020 Jan 29;12(2):1685-1703. doi: 10.18632/aging.102707.
IL-33 is an important member of the IL-1 family which has pleiotropic activities in innate and adaptive immune responses. Recently, some researchers have focused on the function of cellular immunity in the development of tumor. The biological role of IL-33 in glioma is poorly understood. In this study, we showed that glioma cells and tissues expressed higher levels of IL-33 and its receptor ST2 compared to normal brain. Clinically, IL-33 expression was associated with poor survival in patients with glioma. Administration of human IL-33 enhanced cell migration, invasion, epithelial to mesenchymal transition and stemness. Anti-ST2 blocked these effects of IL-33 on tumor. Mechanistically, IL-33 activated JNK signaling pathway via ST2 and increased the expression of key transcription factors that controlled the process of EMT and stemness. Moreover, IL-33 prevented temozolomide induced tumor apoptosis. Anti-ST2 or knockdown IL-33 increased the sensitivity of tumor to temozolomide. Thus, targeting the IL-33/ST2 axis may offer an opportunity to the treatment of glioma patients.
IL-33 是 IL-1 家族的重要成员，在先天和适应性免疫反应中具有多种活性。最近，一些研究人员关注细胞免疫在肿瘤发展中的作用。IL-33 在神经胶质瘤中的生物学作用知之甚少。在这项研究中，我们表明神经胶质瘤细胞和组织表达更高水平的 IL-33 和其受体 ST2，与正常大脑相比。临床上，IL-33 的表达与神经胶质瘤患者的不良预后相关。人 IL-33 的给药增强了细胞迁移、侵袭、上皮间质转化和干性。抗 ST2 阻断了 IL-33 对肿瘤的这些作用。在机制上，IL-33 通过 ST2 激活 JNK 信号通路，并增加了控制 EMT 和干性过程的关键转录因子的表达。此外，IL-33 可阻止替莫唑胺诱导的肿瘤细胞凋亡。抗 ST2 或敲低 IL-33 增加了肿瘤对替莫唑胺的敏感性。因此，靶向 IL-33/ST2 轴可能为神经胶质瘤患者的治疗提供机会。
