文章：

生长分化因子15在胶质母细胞瘤干细胞中的过表达促进其放射抗性

Overexpression of Growth Differentiation Factor 15 in Glioblastoma Stem Cells Promotes Their Radioresistance

原文发布日期：20 December 2023

DOI: 10.3390/cancers16010027

类型: Article

开放获取: 是

英文摘要：

GSCs play an important role in GBM recurrence. Understanding the resistance mechanisms in these cells is therefore crucial for radiation therapy optimization. In this study, using patient-derived GSCs, we demonstrate that GDF15, a cytokine belonging to the TGF-β superfamily, is regulated by irradiation (IR) and the transcription factor WWTR1/TAZ. Blocking WWTR1/TAZ using specific siRNAs significantly reduces GDF15 basal expression and reverses the upregulation of this cytokine induced by IR. Furthermore, we demonstrate that GDF15 plays an important role in GSC radioresistance. Targeting GDF15 expression by siRNA in GSCs expressing high levels of GDF15 sensitizes the cells to IR. In addition, we also found that GDF15 expression is critical for GSC spheroid formation, as GDF15 knockdown significantly reduces the number of GSC neurospheres. This study suggests that GDF15 targeting in combination with radiotherapy may be a feasible approach in patients with GBM.

摘要翻译： 

胶质瘤干细胞在胶质母细胞瘤复发过程中发挥重要作用。因此，理解这些细胞的耐药机制对于优化放射治疗至关重要。本研究利用患者来源的胶质瘤干细胞，证实了属于TGF-β超家族的细胞因子GDF15受到放射线照射及转录因子WWTR1/TAZ的调控。使用特异性siRNA阻断WWTR1/TAZ可显著降低GDF15的基础表达水平，并逆转放射线照射诱导的该细胞因子上调。进一步研究发现，GDF15在胶质瘤干细胞放射抵抗中起关键作用。通过siRNA靶向抑制高表达GDF15的胶质瘤干细胞中该因子表达，可显著增强细胞对放射线的敏感性。此外，我们还发现GDF15表达对胶质瘤干细胞球体形成至关重要，敲低GDF15能显著减少胶质瘤干细胞神经球数量。本研究表明，针对GDF15的靶向治疗联合放疗可能是胶质母细胞瘤患者的可行治疗策略。

原文链接：

Overexpression of Growth Differentiation Factor 15 in Glioblastoma Stem Cells Promotes Their Radioresistance