瘤培养的Gr1+CD11b+细胞通过OSM/IL-6/JAK诱导的癌细胞可塑性驱动乳腺癌转移
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Sanam Peyvandi1, Manon Bulliard1, Alev Yilmaz1
1Pathology Unit, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
The Journal of clinical investigation
|January 18, 2024
概括
乳腺癌细胞通过瘤微环境信号驱动的可塑性变得更加转移. 哥斯塔丁M和IL-6调解这种转化,为转移提供潜在的治疗点.
科学领域:
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
- 转移研究研究 转移研究
背景情况:
- 癌细胞的可塑性驱动治疗阻力和转移,这是癌症死亡的主要原因.
- 瘤微环境是癌细胞可塑性和转移潜力的关键调节者.
- 了解瘤衍生的线索对于开发对抗转移性乳腺癌的策略至关重要.
研究的目的:
- 研究瘤微环境诱导乳腺癌细胞可塑性和转移的机制.
- 为了确定特定的分子通路和细胞群,参与促进转移潜力.
主要方法:
- 利用实验性乳腺癌模型和转录基因分析.
- 研究了干细胞抗原-1阳性 (SCA1+) 和瘤培养的Gr1+CD11b+ (Tu-Gr1+CD11b+) 细胞的作用.
- 评估了在体外和体外对细胞可塑性和转移的上素M (OSM),IL-6和JAK抑制的影响.
主要成果:
- 在瘤进展过程中丰富的SCA1+细胞表现出增加的干细胞样性质和转移能力.
- 图-Gr1+CD11b+细胞通过OSM和IL-6将低转移性SCA1-细胞转化为高度转移性SCA1+细胞.
- JAK抑制阻断了OSM/IL-6诱导的SCA1+丰富,而OSM/IL-6耗尽则抑制了转移.
- 通过化疗选择的4T1细胞通过自身隐性IL-6保持了SCA1+阳性,而这种阳性通过JAK抑制被逆转.
- 在乳腺癌患者中,Tu-Gr1+CD11b+细胞诱导了一种与生存率低下和肺转移增加相关的基因特征.
结论:
- 确定了涉及OSM/IL-6/JAK的关键的副/自身轴,该轴驱动乳腺癌细胞可塑性和转移.
- 这一途径代表了管理转移性乳腺癌的临床相关目标.
- 瘤培养的髓状细胞在促进乳腺癌细胞可塑性和扩散方面发挥着重要作用.
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