Impact of hypoxia on the molecular content of glioblastoma-derived exosomes

Simona Di Giulio, E. Carata, Marco Muci, S. Mariano, E. Panzarini
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Abstract

Hypoxia is a pathologic condition characterized by a tissue oxygen deficiency due to either decreased oxygen intake from outside and/or disruption of oxygen utilization in cells. This condition may arise when the oxygen demand exceeds its supply or the partial pressure of oxygen is below 10 mmHg. This situation poses a significant problem for glioblastoma (GBM) patients as it can activate angiogenesis, increase invasiveness and metastatic risk, prolong tumor survival, and suppress anti-tumor immunity, making hypoxic cells resistant to radiotherapy and chemotherapy. Low oxygen levels in tumors can cause severe cellular changes that can affect the release of extracellular vesicles (EVs), especially exosomes (EXOs), altering their proteomic profile both qualitatively and quantitatively. EXOs represent an adaptive response to hypoxic stress; therefore, they can be used to determine oxygen levels in cancer and assess its aggressiveness. They not only release signaling molecules to attract cells that promote the formation of small vessel walls but also send signals to other tumor cells that trigger their migration, which in turn plays a crucial role in the formation of metastases under hypoxia. This review investigates how the molecular profile of GBM-derived exosomes changes under hypoxic conditions, offering future possibilities for noninvasive diagnosis and monitoring of brain tumor patients.
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缺氧对胶质母细胞瘤外泌体分子含量的影响
缺氧是一种病理状态,其特征是由于从外界摄入的氧气减少和/或细胞内氧气利用的中断导致组织缺氧。当氧气供不应求或氧分压低于 10 mmHg 时,就会出现这种情况。这种情况给胶质母细胞瘤(GBM)患者带来了严重问题,因为它会激活血管生成,增加侵袭性和转移风险,延长肿瘤存活时间,抑制抗肿瘤免疫,使缺氧细胞对放疗和化疗产生抗药性。肿瘤中的低氧水平会导致严重的细胞变化,从而影响细胞外囊泡 (EV) 的释放,尤其是外泌体 (EXO),从质和量两方面改变其蛋白质组学特征。外泌体代表了对缺氧压力的一种适应性反应;因此,它们可用于确定癌症中的氧含量并评估其侵袭性。它们不仅释放信号分子吸引细胞,促进小血管壁的形成,而且还向其他肿瘤细胞发出信号,引发它们的迁移,这反过来又在缺氧条件下形成转移灶方面发挥了关键作用。这篇综述探讨了 GBM 衍生外泌体的分子特征在缺氧条件下是如何变化的,为未来无创诊断和监测脑肿瘤患者提供了可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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