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文章:

细胞外囊泡与线粒体靶向调控非小细胞肺癌放疗应答:挑战与展望

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

原文发布日期:15 June 2024

DOI: 10.3390/cancers16122235

类型: Article

开放获取: 是

 

英文摘要:

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC.

 

摘要翻译: 

在细胞生命周期中,细胞外囊泡(EVs)运输着包括细胞器、蛋白质、RNA、DNA、代谢物等在内的不同货物,这些货物能够影响受体细胞的增殖与凋亡。来自转移性癌细胞的EVs能够重塑肿瘤微环境(TME)中的细胞外基质及细胞,促进肿瘤侵袭并协助转移前微环境的形成。尽管这一过程尚未被完全阐明,但有证据表明EVs能够促进细胞间的遗传物质传递。在非小细胞肺癌(NSCLC)背景下,EVs可通过不同机制介导细胞间线粒体(Mt)转移,递送线粒体细胞器(MtO)、线粒体DNA(mtDNA)和/或线粒体RNA/蛋白质特征性物质(MtS)。另一方面,某些癌细胞群体主要通过隧道纳米管(TNTs)劫持肿瘤微环境细胞中的MtO。这种转移有助于恢复线粒体功能,使代谢受损的良性细胞获益,并恢复其代谢活性。然而,在癌症中转移线粒体成分与移植完整线粒体细胞器所产生的影响仍不明确,且存在学术争议。部分研究表明,EV介导的线粒体递送至癌细胞可能影响肿瘤对放射治疗的反应性,可能增强其放射抵抗性或放射敏感性。在本综述中,我们旨在指出当前围绕实验数据存在的争议,并着重探讨放射治疗领域可能突破非小细胞肺癌耐药机制的新型范式转变策略。

 

原文链接:

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

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