恶性细胞分泌的化学因子通过内皮细胞激活驱动结直肠癌的进展
Xiaohan Guo1, Yichun Huang2, Yuxuan Sun1
1West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, 610041, Chengdu, People's Republic of China.
大肠直肠癌 (CRC) 的进展涉及瘤微环境 (TME) 的变化. 先进的CRC阶段显示恶性细胞分泌CXCL2,这刺激ACKR1对内皮细胞,促进入侵和转移.
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:
- 瘤微环境 (TME) 显著影响结直肠癌 (CRC) 的进展和免疫反应.
- 了解TME动态对于开发有效的CRC疗法至关重要.
研究的目的:
- 研究不同阶段 (T2,T3,T4a) 的CRC患者的TME动态.
- 确定驱动瘤入侵和转移的关键分子机制在先进的CRC.
主要方法:
- 综合单细胞RNA测序 (scRNA-seq),对拷贝数变异的推断 (inferCNV) 和非负矩阵因子化 (NMF).
- 对26名CRC患者的TME分析,按T阶段分层.
- 基因表达分析和功能验证通过基因淘汰实验.
主要成果:
- 晚期T4aCRC阶段的恶性细胞表现出明显的与免疫相关的模式.
- 调节化学反应的基因,包括CXCL1,CXCL2,CXCL3和GDF15,表现出与瘤入侵相关的阶段依赖的表达变化.
- 鉴定出CXCL2-ACKR1轴,涉及恶性细胞中的CXCL2和内皮细胞上的ACKR1,是癌细胞迁移和入侵的关键驱动因素.
结论:
- 晚期CRC中恶性细胞增加CXCL2分泌刺激内皮细胞上的ACKR1,促进瘤入侵和转移.
- 针对ACKR1-CXCL2相互作用,为局部发达的CRC提供了潜在的治疗策略,以阻止转移.
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