由EMT驱动的可塑性有望增加细胞变异性,以促进乳腺癌的治疗适应性
Lauriane Muller1, Frédérique Fauvet2, Christelle Chassot2
1Integrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon, France.
Cancer cell international
|February 3, 2025
概括
细胞可塑性,由上皮-介质细胞过渡 (EMT) 驱动,增加癌细胞多样性和丰富干细胞,可能有助于化疗耐药性. 在治疗前针对这种多样性对于高可塑性瘤至关重要.
科学领域:
- 癌症生物学 癌症生物学
- 细胞可塑性 细胞可塑性
- 瘤微环境 瘤微环境
背景情况:
- 细胞可塑性允许癌细胞在非遗传上适应,阻碍治疗结果.
- 表皮-介质细胞过渡 (EMT) 是一种关键的可塑性机制,与癌症耐药性和转移有关.
- 对于EMT在人口多样性中的确切作用及其在化疗期间的动态仍然不清楚.
研究的目的:
- 研究EMT驱动的可塑性对化学疗法下三阴性乳腺癌 (TNBC) 的表型多样性动态的影响.
- 为了确定EMT驱动的可塑性是否丰富特定细胞群,如干细胞.
- 探索治疗前细胞状态与患者存活率之间的相关性.
主要方法:
- 利用单细胞转录组学来分析两个体外TNBC模型中的表型多样性,其中包括诱导或自发EMT.
- 量化细胞-细胞变异性和干细胞样细胞丰富,以应对化疗.
- 相关的遗传/表型变异性和已识别的预先适应的细胞种群.
主要成果:
- 由EMT驱动的可塑性显著增加了表型细胞细胞的变异性,并为干细胞类细胞丰富 (p < 0.001).
- 高可塑性种群在治疗前显示出更多的预先适应的细胞 (p = 0.03).
- 在自发EMT模型中,预先适应的细胞 (罕见异常值) 与接受化疗的TNBC患者的生存率改善相关 (p = 0.03).
结论:
- 由EMT驱动的可塑性促进了未来的多样化,增加了人口的表型多样性,并在治疗前产生了罕见的预先适应状态.
- 这种多样化可能会导致高可塑性瘤的化疗耐药性.
- 在治疗前准表型多样性是高可塑性癌症的潜在治疗策略.
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