在单细胞水平上,乳腺癌循环瘤细胞的表皮细胞-介质细胞过渡相关异质性的特征
Justyna Topa1,2, Julia Richert1, Tomasz Stokowy3,4
1Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical Univeristy of Gdańsk, Medical University of Gdańsk, Poland.
Molecular oncology
|October 5, 2025
概括
在早期乳腺癌 (BC) 中检测多种循环瘤细胞 (CTC) 揭示了与疾病传播相关的异质性. 中细胞CTC显示翻译减少,为BC传播提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 表皮-介质细胞过渡 (EMT) 创造了循环瘤细胞 (CTC) 的多样性,影响了癌症传播的检测和理解.
- 在早期乳腺癌 (BC) 中检测CTC是具有挑战性的,因为它们的稀有性和异质性.
研究的目的:
- 在BC患者的血液样本中检测和描述具有不同EMT状态的CTC.
- 研究不同CTC表型的生物特性和传播模式.
主要方法:
- 来自107个BC患者的血液样本使用免疫磁性衰竭和多标志物免疫光分析.
- 使用单细胞转录组学来分析检测到的CTC.
- 表型包括表皮 (eCTC),表皮-介质细胞 (emCTC),介质细胞 (mCTC) 和混合表型.
主要成果:
- 在51.9%的前不治疗的早期BC病例中检测到CTC,其中有很大比例是eCTC,emCTC,mCTC和混合表型.
- 与光线BC (17%) 相比,三阴BC (86%) 的CTC异质性更为普遍.
- 淋巴结参与预测了CTC传播,而瘤大小与mCTC丰富度相关. 介酶体CTC表现出下调的核糖体基因和抑制的翻译,与mTORC1信号相关.
结论:
- 乳腺癌CTC表现出不同的EMT状态,其中介质细胞表型显示出明显的分子特征.
- CTC异质性和特定的表型与瘤亚型和淋巴结状况等临床因素有关.
- 针对中细胞CTC漏洞,如翻译抑制,可能为管理BC转移提供新的治疗策略.
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