内皮细胞铁突变影响复发性多形性胶质母细胞瘤患者的IDH野生型胶质母细胞瘤生长

IF 1.9 4区 医学 Q2 BIOLOGY
Bo Liang, Xinghuan Ding, Siyuan Yang, Enshan Feng
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引用次数: 0

摘要

众所周知,胶质母细胞瘤的临床预后较差,与原发性肿瘤相比,复发性肿瘤往往表现出更大的侵袭性和更快的生长速度。为了了解导致这一现象的瘤内变化,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的铁突变上调,NOX4 基因的显著过表达证实了这一点。进一步的分析表明,敲除内皮细胞中的 NOX4 会降低铁氧化途径的活性。利用铁突变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有所下降。这些结果突显了铁凋亡在肿瘤中的复杂作用,并表明在治疗胶质母细胞瘤时,以铁凋亡为靶点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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Endothelial cell ferroptosis influences IDH wild-type glioblastoma growth in recurrent glioblastoma multiforme patients.

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.

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来源期刊
CiteScore
4.00
自引率
0.00%
发文量
129
审稿时长
2 months
期刊介绍: The Brazilian Journal of Medical and Biological Research, founded by Michel Jamra, is edited and published monthly by the Associação Brasileira de Divulgação Científica (ABDC), a federation of Brazilian scientific societies: - Sociedade Brasileira de Biofísica (SBBf) - Sociedade Brasileira de Farmacologia e Terapêutica Experimental (SBFTE) - Sociedade Brasileira de Fisiologia (SBFis) - Sociedade Brasileira de Imunologia (SBI) - Sociedade Brasileira de Investigação Clínica (SBIC) - Sociedade Brasileira de Neurociências e Comportamento (SBNeC).
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