Radiation-Induced Bystander Effect on the Genome of Bone Marrow Mesenchymal Stem Cells in Lung Cancer
Radiation-Induced Bystander Effect on the Genome of Bone Marrow Mesenchymal Stem Cells in Lung Cancer
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DOI：
10.1089/ars.2022.0072
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发表时间：
2022-12-02
影响因子：
6.6
通讯作者：
Liu，Yong-Qi
中科院分区：
文献类型：
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作者：
Zhang，Yi-Ming;Zhang，Li-Ying;Liu，Yong-Qi
目的：辐射副辐射效应（里贝）可诱导肺癌癌旁骨髓间充质干细胞（BMSCs）基因组不稳定，这种效应不仅存在于短期，而且长期伴随，但其具体机制尚不清楚。本研究的目的是探讨短期和长期里贝诱导肿瘤相关BMSCs基因组损伤机制的异同，为临床不同时期里贝的辅助保护药物提供理论依据。短期里贝后，肿瘤相关BMSCs中TGF-β1、TNF-α和HIF-1α的表达增加，而长期里贝后，只有TNF-α和HIF-1α的表达增加。我们进一步证实了基因组不稳定性与HIF-1α通路的激活有关，并且这是由TNF-α和TGF-β1介导的。此外，我们发现在所考虑的里贝分析窗口中基因组不稳定性机制的差异。在短期里贝损伤中，TNF-α和TGF-β1均起作用，而在长期里贝损伤中，只有TNF-α起决定性作用。此外，不同组织的BMSC募集和基因组不稳定性存在差异，肿瘤和骨髓中的表达比肺中的表达更明显。创新与结论：在短期和长期里贝过程中，我们可以显示细胞因子TGF-β1和TNF-α表达的动态变化。两者的差异表达是在所考虑的分析窗口内引起肿瘤相关BMSCs基因组损伤的关键。因此，这些结果可作为指导在不同的临床阶段的辐射防护辅助药物的管理。Redox Signal.38，747-767.
Aims:Radiation by-radiation effect (RIBE) can induce the genomic instability of bone marrow mesenchymal stem cells (BMSCs) adjacent to lung cancer, and this effect not only exists in the short-term, but also accompanies it in the long-term, but its specific mechanism is not clear. Our goal is to explore the similarities and differences in the mechanism of genomic damage in tumor-associated BMSCs induced by short-term and long-term RIBE, and to provide a theoretical basis for adjuvant drugs for protection against RIBE at different clinical time periods.Results:We found that both short- and long-term RIBE induced genomic instability. We could show a high expression of TGF-β1, TNF-α, and HIF-1α in tumor-associated BMSCs after short-term RIBE whereas only TNF-α and HIF-1α expression was increased in long-term RIBE. We further confirmed that genomic instability is associated with the activation of the HIF-1α pathway and that this is mediated by TNF-α and TGF-β1. In addition, we found differences in the mechanisms of genomic instability in the considered RIBE windows of analysis. In short-term RIBE, both TNF-α and TGF-β1 play a role, whereas only TNF-α plays a decisive role in long-term RIBE. In addition, there were differences in BMSC recruitment and genomic instability of different tissues with a more pronounced expression in tumor and bone marrow than compared to lung.Innovation and Conclusion:We could show dynamic changes in the expression of the cytokines TGF-β1 and TNF-α during short- and long-term RIBE. The differential expression of the two is the key to causing the genomic damage of tumor-associated BMSCs in the considered windows of analysis. Therefore, these results may serve as a guideline for the administration of radiation protection adjuvant drugs at different clinical stages.Antioxid. Redox Signal.38, 747–767.