透瘤的细菌破坏癌症上皮细胞的相互作用,并诱导细胞循环停止
Jorge Luis Galeano Niño1, Falk Ponath2, Victor A Ajisafe3
1Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA.
Cancer cell
|October 17, 2025
概括
细胞外细菌,如Fusobacterium,通过破坏细胞接触,促进癌细胞休眠和5-甲抗性. 这种微生物与瘤的相互作用重塑了瘤的微环境,并影响了治疗反应.
科学领域:
- 微生物学 微生物学
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
背景情况:
- 透瘤的细菌会影响癌症的进展和治疗耐药性.
- 细菌调节癌细胞行为的特定机制尚未完全理解.
研究的目的:
- 阐明包括Fusobacterium在内的细胞外内细菌影响癌症上皮细胞行为的机制.
- 为了研究fusobacterium,癌细胞静止和化学抵抗之间的联系.
主要方法:
- 空间成像和单细胞空间转录学被用来分析细菌局部化和宿主细胞转录状态.
- 用Fusobacterium nucleatum进行了体外实验,以评估对上皮细胞的影响.
- 验证包括活细胞成像,空间分析,小鼠模型和患者队列 (结肠直肠癌和直肠癌) 的分析.
主要成果:
- 细胞外细菌,特别是Fusobacterium,在结肠直肠和口腔癌中的静止瘤微细菌中被发现.
- Fusobacterium nucleatum诱导了表皮细胞循环停止 (G0-G1) 和体外转录静止,从而产生对5-甲的耐药性.
- 转录组分析揭示了细菌丰富地区的细胞周期,转录和抗原呈现基因的下调,这表明一种免疫逃避型表型.
- 在直肠癌队列中,高的Fusobacterium负担与减少的治疗反应相关.
结论:
- 细胞外细菌促进癌细胞静止和化学抵抗.
- 微生物与瘤的相互作用是提高癌症治疗疗效的潜在治疗标.
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