Department of Neurosurgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Braz J Med Biol Res. 2024 Jul 8;57:e13961. doi: 10.1590/1414-431X2024e13961. eCollection 2024.
Glioblastomas are known for their poor clinical prognosis, with recurrent tumors often exhibiting greater invasiveness and faster growth rates compared to primary tumors. To understand the intratumoral changes driving this phenomenon, we employed single-cell sequencing to analyze the differences between two pairs of primary and recurrent glioblastomas. Our findings revealed an upregulation of ferroptosis in endothelial cells within recurrent tumors, identified by the significant overexpression of the NOX4 gene. Further analysis indicated that knocking down NOX4 in endothelial cells reduced the activity of the ferroptosis pathway. Utilizing conditioned media from endothelial cells with lower ferroptosis activity, we observed a decrease in the growth rate of glioblastoma cells. These results highlighted the complex role of ferroptosis within tumors and suggested that targeting ferroptosis in the treatment of glioblastomas requires careful consideration of its effects on endothelial cells, as it may otherwise produce counterproductive outcomes.
胶质母细胞瘤的临床预后较差，复发性肿瘤通常比原发性肿瘤具有更强的侵袭性和更快的生长速度。为了了解驱动这一现象的肿瘤内变化，我们采用单细胞测序技术分析了两对原发性和复发性胶质母细胞瘤之间的差异。我们的研究结果表明，复发性肿瘤内皮细胞中的铁死亡途径被显著上调，这是由 NOX4 基因的显著过表达所导致的。进一步的分析表明，敲低内皮细胞中的 NOX4 可降低铁死亡途径的活性。利用铁死亡活性较低的内皮细胞的条件培养基，我们观察到胶质母细胞瘤细胞的生长速度降低。这些结果强调了铁死亡在肿瘤中的复杂作用，并表明在胶质母细胞瘤的治疗中靶向铁死亡需要仔细考虑其对内皮细胞的影响，否则可能会产生适得其反的结果。
