缺血性损伤通过加速造血衰老驱动新生的瘤生长
Alexandra A C Newman1, José Gabriel Barcia Durán2, Richard Von Itter2
1Cardiovascular Research Center, Department of Medicine, New York University Langone Health, New York, New York, USA; Leon H. Charney Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA. Electronic address: https://twitter.com/aacnewman13.
JACC. CardioOncology
|August 21, 2025
概括
通过改变造血干细胞 (HSPC),促进骨髓细胞的产生和抑制抗瘤免疫力,加速乳腺癌的生长. 这些变化是持久的,可以传播,影响癌症的进展.
科学领域:
- 心血管生物学
- 癌症生物学
- 免疫学
- 干细胞生物学
背景情况:
- 周围动脉疾病 (PAD) 增加了癌症风险,血液形成干细胞和前代细胞 (HSPCs) 的与衰老相关的变化与心血管疾病和癌症有关.
- 改变血液形成在心血管疾病驱动的瘤进展中的具体作用尚不清楚.
研究的目的:
- 在外周缺血和相关的骨髓部位变化后调查瘤生长.
- 通过改变的造血促进癌症发展和进展的机制.
主要方法:
- 在后肢缺血 (HLI) 或假手术后监测小鼠的乳腺癌生长.
- 使用流细胞计量评估瘤免疫微环境,循环免疫细胞和HSPC区.
- 在骨髓原始体上进行单细胞RNA和ATAC测序以分析转录和表观遗传变化.
- 使用骨髓移植来检查因缺血引起的HSPC重编程对瘤进展的功能影响.
主要成果:
- 周围缺血增加单细胞和中性细胞的产生,同时减少淋巴细胞,由转向骨髓偏差HSPC驱动.
- 观察到癌症增长加速,瘤富含髓状细胞和调节性T细胞.
- 转录和表观遗传分析显示,在HLI和瘤存在后,单细胞/树突前代的炎症和衰老相关特征.
- 由HLI诱导的瘤生长加速和骨髓歪曲是通过骨髓移植传播的,这表明先天免疫的持续重新编程.
结论:
- 周围缺血会加剧造血干细胞的炎症.
- 抗瘤免疫力的长期改变有助于加速乳腺瘤的生长.
- 缺血引起的血液形成重编程是促进癌症进展的重要机制.
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