单细胞转录组分析确定衰老的骨细胞是导致乳腺癌转移的骨破坏的因素
Manish Adhikari1, Japneet Kaur1, Hayley M Sabol1
1Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, US.
Research square
|April 1, 2024
概括
乳腺癌骨转移导致骨细胞变老,促进骨的破坏. 用老化剂清除这些衰老细胞,在小鼠中保留了骨质,这表明了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 骨生物学 骨生物学 骨生物学
- 细胞衰老 细胞衰老
背景情况:
- 乳腺癌骨转移导致严重的发病率和死亡率,增加骨折风险.
- 骨的瘤细胞殖民重新编程了微环境,破坏了骨重塑,并导致病变.
- 这种重编程对嵌入矩阵骨细胞的影响尚不清楚.
研究的目的:
- 为了研究骨细胞在乳腺癌骨转移中的作用.
- 为了确定骨细胞是否经历衰老并导致骨破坏.
- 探索老化疗法作为骨转移的潜在治疗方法.
主要方法:
- 来自具有骨转移的小鼠骨细胞的单细胞RNA测序.
- 多复合在位混合化和人工智能辅助分析在小鼠和人类患者中.
- 在体外和体外器官培养模型.
- 在小鼠模型中使用老年化药物的治疗.
主要成果:
- 乳腺癌骨转移中的骨细胞表现出过早衰老和与衰老相关的分泌表型 (SASP).
- 这些衰老的骨细胞表达了亲骨类细胞的基因,有利于骨的破坏.
- 乳腺癌细胞诱导骨细胞衰老,并增强其骨质结晶的潜力.
- 在老鼠中,老化疗法减少了骨质再吸收,并保持了骨质.
结论:
- 骨细胞衰老是对乳腺癌细胞殖民的病态反应,有助于骨破坏.
- 在临床前的模型中,老化疗法清除了衰老细胞,抑制了骨质再吸收,并保持了骨质质量.
- 准骨细胞衰老是乳腺癌骨转移的一个有希望的治疗策略.
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