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来自骨髓瘤细胞的细胞外囊包装S100A11通过招募gMDSCs来调解肺前转移性利基形成
Chuangzhong Deng1, Yanyang Xu1, Hongmin Chen1
1Department of Musculoskeletal Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China; State Key Laboratory of Oncology in Southern China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
Cell reports
|February 11, 2024
概括
骨髓瘤瘤细胞使用细胞外囊泡 (EVs) 创建肺前转移性利基 (PMN),这些囊泡会吸引免疫抑制的粒细胞髓衍生抑制细胞 (gMDSCs). 这一过程是由S100A11在EV中驱动的,促进肺转移和不良预后.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 前转移性位 (PMN) 促进器官特异性转移.
- 在骨髓瘤中肺特异性热带的机制尚不清楚.
- 了解瘤-肌瘤相互作用对于转移研究至关重要.
研究的目的:
- 研究免疫细胞在骨髓瘤肺部PMN中的作用.
- 为了定义原发性骨髓瘤细胞和肺 stromal 细胞之间的交叉.
- 为了确定驱动骨髓瘤肺转移的分子机制.
主要方法:
- 在肺PMNs中分析免疫细胞组成.
- 研究骨髓瘤细胞衍生的细胞外囊泡 (EVs) 和它们的载荷.
- 电动汽车的蛋白质学概况.
- 评估巨细胞中信号通路 (JAK2/STAT3) 的激活.
- 关联分子标记与患者预后.
主要成果:
- 颗粒细胞髓质衍生抑制细胞 (gMDSCs) 是肺PMN中的关键免疫细胞.
- 骨髓瘤EVs通过CXCL2分泌激活肺间歇性巨细胞.
- EV包装的S100A11通过与USP9X交互激活巨细胞中的JAK2/STAT3通路.
- 高S100A11表达和循环的gMDSC与肺转移和不良预后相关.
结论:
- 来自瘤的EVs通过招募gMDSC来编排肺PMN的形成.
- 电动汽车中的S100A11是这一过程的关键调解者.
- 这一途径代表了预防骨髓瘤肺转移的潜在治疗标.
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