胶质母细胞瘤以其临床预后不良而闻名，与原发性肿瘤相比，复发性肿瘤通常表现出更大的侵袭性和更快的生长速度。为了了解驱动这种现象的瘤内变化，我们采用单细胞测序来分析两对原发性和复发性胶质母细胞瘤之间的差异。我们的研究结果揭示了复发性肿瘤内皮细胞铁死亡的上调，这是通过 NOX4 基因的显着过度表达来确定的。进一步分析表明，敲低内皮细胞中的 NOX4 会降低铁死亡途径的活性。利用具有较低铁死亡活性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率下降。这些结果强调了铁死亡在肿瘤内的复杂作用，并表明在治疗胶质母细胞瘤时针对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。

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.