来自瘤的循环DNA可以在小鼠胚胎纤维细胞中诱导衰老和SASP激活
1Department of Medical Biology, Faculty of Medicine, Kırşehir Ahi Evran University, Kırşehir, 40100, Turkey. ekin.celik@ahievran.edu.tr.
Biogerontology
|February 5, 2026
概括
循环瘤DNA (ctDNA) 可以诱导健康细胞的压力反应,促进衰老. 这表明ctDNA可能通过影响正常的树皮细胞来改变瘤的微环境.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 循环瘤DNA (ctDNA) 是癌症诊断和治疗中的一个关键生物标志物.
- 对于ctDNA对正常 stromal 细胞的生物学影响尚不清楚.
- 来自瘤的核酸可能会影响瘤的微环境.
研究的目的:
- 研究ctDNA对正常纤维细胞的生物学影响.
- 为了确定ctDNA是否可以在健康细胞中诱导应激反应,如衰老.
- 探索ctDNA在改变瘤微环境中的潜在作用.
主要方法:
- 从黑色素瘤和纤维细胞培养物中分离出ctDNA和无细胞DNA (cfDNA).
- 小鼠胚胎纤维细胞 (MEFs) 用不同度的ctDNA和cfDNA进行了处理.
- 使用SA-β-Gal染色和定量PCR对与衰老相关的基因 (p16,p21,p53) 和SASP因子 (IL-6,IL-1β) 进行衰老评估.
主要成果:
- ctDNA治疗导致老化标志物和SASP细胞因子产生剂量依赖的增加.
- 在ctDNA处理的细胞中观察到SA-β-Gal染色的升高.
- 与对照组相比,cfDNA治疗没有引起衰老标志物或SASP因子的显著变化.
结论:
- ctDNA作为一种生物活跃的刺激,可以诱导正常纤维细胞的衰老类反应.
- 来自瘤的细胞外核酸可能会导致瘤微环境中的肌体细胞行为发生变化.
- 这些发现突出了瘤可以影响周围环境的新机制.
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