在结直肠癌细胞迁移中解离化学和机械信号
Maxwell G Tetrick1, Md Abul Bashar Emon2, Umnia Doha2
1Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Scientific reports
|February 10, 2025
概括
癌症相关纤维细胞 (CAFs) 影响结肠直肠癌转移. 机械信号,而不是化学信号,驱动HCT-116细胞迁移,特别是在3D环境中的高密度.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 结肠直肠癌 (CRC) 转移受瘤微环境信号的影响.
- 癌症相关纤维细胞 (CAFs) 在调节化学和机械线索方面发挥着关键作用.
- 了解化学和机械信号之间的相互作用对于向转移至关重要.
研究的目的:
- 在HCT-116细胞迁移中区分化学信号和机械信号的作用.
- 研究CAFs对HCT-116细胞迁移的影响.
- 确定主导信号通路 (化学与机械) 驱动CRC细胞迁移.
主要方法:
- 使用了HCT-116结肠癌细胞和CAFs.
- 用化学吸引剂 (CXCL12,TGF-β,Activin A) 和CAF受条件介质进行了二维透孔测定.
- 采用3D原基质测试来评估在机械应力和共同培养条件下的迁移.
主要成果:
- 单独的化学吸引剂和CAF调节的介质在低密度下没有增强HCT-116迁移.
- 在2D跨井测定中与CAF共同培养增加了HCT-116迁移,表明密度或相互信号依赖.
- 在高密度的3D矩阵中,HCT-116细胞显示出沿机械应力轴的增强迁移,独立于应变源.
- 发现机械信号在3D共同培养中主导HCT-116迁移,而不是化学线索.
结论:
- HCT-116细胞迁移主要由机械信号驱动,特别是在3D环境中的高细胞密度下.
- 瘤微环境的机械特性显著影响结直肠癌细胞转移.
- 在2D模型中,化学吸引剂诱导的迁移可能需要相互信号或高细胞密度.
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