在三阴性乳腺癌进展期间,HSP90促进瘤相关的巨细胞分化
Lingjia Hong1, Manami Tanaka1, Masato Yasui1
1Department of Pharmacology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Scientific reports
|September 28, 2024
概括
热冲击蛋白90 (HSP90) 抑制阻断瘤相关巨细胞 (TAM) 在三阴性乳腺癌 (TNBC) 的分化. 这表明HSP90是TNBC免疫治疗的潜在治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 对癌症进展至关重要.
- TAMs的差异化机制在很大程度上是未知的.
- 三阴性乳腺癌 (TNBC) 是一个重大的治疗挑战.
研究的目的:
- 调查TNBC微环境中驱动单细胞分化成TAM的因素.
- 为了确定TNBC免疫治疗的潜在治疗点.
主要方法:
- 对172种化合物的选,以检测它们对单细胞到TAM分化的影响.
- 使用THP-1人类单细胞和TNBC衍生条件介质 (CM).
- 评估细胞信号通路 (MAPK,AKT,STAT3) 和基因/蛋白质表达.
- 使用小鼠瘤模型进行体内研究.
主要成果:
- 一种热冲击蛋白90 (HSP90) 抑制剂有效地阻止了TNBC诱导的单细胞到TAM分化.
- TNBC-CM激活了关键信号通路和TAM相关的标记物,这些标记物被HSP90抑制抑制.
- 由TNBC分泌的细胞外HSP90促进了TAM分化.
- 在小鼠模型中,HSP90抑制抑制了瘤生长并减少了TAMs.
结论:
- 在TNBC微环境中,HSP90在调节单细胞分化成TAM中起着至关重要的作用.
- 向HSP90通过调节TAM分化,为TNBC免疫疗法提供了一个有希望的策略.
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