单细胞转录组测序揭示了SPP1-CD44介导的巨细胞和瘤细胞相互作用驱动TNBC中的化学抵抗
Fuzhong Liu1, Junfeng Zhang1, Xiaowei Gu1
1Xinjiang Medical University Affiliated Cancer Hospital, Urumqi, China.
Journal of cellular and molecular medicine
|July 9, 2024
概括
三阴性乳腺癌 (TNBC) 表现出侵略性行为和耐药性. 与恶性细胞相互作用的SPP1+巨细胞促进这种抗性,表明SPP1+巨细胞是治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 三阴性乳腺癌 (TNBC) 是一种具有高复发率和低生存率的侵袭性亚型.
- 化疗耐药性仍然是TNBC治疗的一个重大挑战.
- 背后的TNBC化学疗法耐药性的机制尚未完全理解.
研究的目的:
- 研究三阴性乳腺癌中化疗耐药性的机制.
- 确定特定的细胞类型和涉及TNBC药物耐药性的分子通路.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 来自化疗敏感和耐药的TNBC患者.
- 对拷贝数变异 (CNV),细胞间相互作用和转录因子的分析.
- 在临床样本上使用多重免疫光学验证.
主要成果:
- 确定了分泌SPP1的SPP1+巨细胞,与恶性细胞CD44.4相互作用.
- 这种相互作用可能会通过恶性细胞中的整蛋白通路激活PDE3B通路,从而赋予抗性.
- 在巨细胞和恶性细胞之间异常增强的SPP1信号与化疗耐药性相关.
结论:
- SPP1+巨细胞及其分泌的SPP1是TNBC化疗耐药性的关键参与者.
- 向SPP1+巨细胞可能提供一种新的治疗策略,以克服TNBC中药物耐药性.
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