扩散到骨髓的乳腺癌通过与CX43相关的瘤-瘤道获得攻击性的表型
Saptarshi Sinha1, Brennan W Callow2, Alex P Farfel2
1Department of Cellular and Molecular Medicine, School of Medicine, UCSD, La Jolla, California, USA.
The Journal of clinical investigation
|October 31, 2024
概括
介酶体 stromal 细胞 (MSCs) 将蛋白质GIV转移到雌激素受体阳性乳腺癌细胞,从而导致侵袭性疾病和耐药性. 这种GIV的细胞间传输策划了比以前理解的更复杂的瘤变化.
科学领域:
- 癌症生物学 癌症生物学
- 细胞相互作用 细胞相互作用
- 分子瘤学分子瘤学
背景情况:
- 雌激素受体阳性 (ER+) 乳腺癌经常转移到骨髓.
- 在ER+乳腺癌细胞和介酶体 stromal 细胞 (MSCs) 之间的相互作用影响癌症的进展.
- 了解这些细胞相互作用对于开发有效的癌症疗法至关重要.
研究的目的:
- 在与MSCs相互作用时,对ER+乳腺癌细胞的接触诱导的分子变化进行全面的目录.
- 为了识别MSC和乳腺癌细胞之间转移的特定分子,影响疾病轨迹.
- 调查蛋白CCDC88A/GIV在调解这些相互作用和驱动侵略性癌症表型中的作用.
主要方法:
- 共同培养ER+乳腺癌细胞和MSCs的模型.
- 综合转录组,蛋白质组和网络分析.
- 候选蛋白质的生物信息优先级.
- 细胞间运输机制的研究,包括道纳米管和连接 43.
- 功能性研究涉及蛋白质重新引入癌细胞.
主要成果:
- 直接的细胞接触,而不是条件介质,诱导了癌细胞中显著的基因和蛋白质表达变化.
- MSCs通过道纳米管将GIV蛋白转移到ER+乳腺癌细胞中,缺乏它.
- 将GIV重新引入GIV阴性乳腺癌细胞模仿了接触诱导变化的方面,赋予了抗雌激素药物耐药性,并增强了瘤扩散.
- 蛋白质与蛋白质相互作用网络突出显示了转移 ("借用") 和瘤内在成分之间的相互作用.
结论:
- 从MSCs到ER+乳腺癌细胞的GIV细胞间传输是驱动侵略性疾病状态的关键机制.
- 转移GIV有助于增长信号自主性和抗雌激素疗法的耐药性.
- 这项研究为MSC-瘤细胞通信提供了多核洞察力,并确定GIV是转移和治疗耐药性的关键调解者.
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