细胞通过调节瘤局部血管和血液动力学来促进转移
Xiaobo Li1,2, Sishan Yan1,2, Xiaoyu Wu1,2
1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou, China.
Nature communications
|August 2, 2025
概括
瘤细胞 (TPC) 调节血液流动和血管泄漏,促进结直肠癌转移. 在TPC中准NKX2-3可以减少血液流动并抑制转移.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 血管生物学 血管生物学
背景情况:
- 血液动力学影响瘤细胞的存活和扩散.
- 血液动力学在瘤细胞输血中的作用在很大程度上是未知的.
- 结肠直肠癌肝脏转移是一个重大的临床挑战.
研究的目的:
- 为了研究血液动力学对结直肠癌转移的影响.
- 为了确定主要瘤血液动力学有助于转移的机制.
- 探索针对瘤血液动力学的治疗策略.
主要方法:
- 在转移性与非转移性结直肠癌患者中对初级瘤血液动力学的比较分析.
- 研究瘤环细胞 (TPC) 亚种群及其与转移的关联.
- 对长非编码RNA NEAT1,NKX2-3和信号通路 (PDE1C/cAMP/PKA) 的分子分析.
- 基因操纵 (Nkx2-3删除) 和TPC中NKX2-3的药理抑制.
- 在临床前模型中评估瘤血管收缩,血流和转移.
主要成果:
- 患有肝转移的结肠直肠癌患者表现出主要瘤直径和血液流量的增加.
- 高NKX2-3瘤周细胞 (TPCs) 的亚群与血液转移有关.
- 富含NEAT1的细胞外囊泡对TPC中的NKX2-3进行上调,抑制流入.
- 在TPC中NKX2-3激活促进瘤血管扩张,增加血液流量和血管泄漏.
- 在TPC中,nkx2-3的删除或药理阻塞会减少瘤的血液流动和转移.
结论:
- 由TPC介导的血管扩张和血液动力学变化是结直肠癌转移的关键驱动因素.
- 在TPC中NKX2-3是瘤血液动力学和转移的关键调节者.
- 在TPC中准NKX2-3提供了潜在的预后标志物和抑制转移的治疗策略.
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