由毛细血管收缩力诱导的核破裂促进了对转移和正常乳腺细胞的差异性影响
Julia Perea Paizal1,2,3, Sam H Au4,5, Chris Bakal6,5
1Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK. jp2219@ic.ac.uk.
Scientific reports
|June 26, 2024
概括
毛细管过境期间的机械力量会在正常和癌细胞中引起核损伤和炎症. 然而,非恶性细胞表现出比转移细胞更显著的转录变化.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 转移性传播涉及循环瘤细胞 (CTC) 导航毛细血管床.
- 毛细血管中遇到的机械力及其对CTC的影响尚未得到充分了解.
研究的目的:
- 研究机械收缩力对恶性和正常乳腺细胞系的影响.
- 了解细胞和分子对毛细血管状收缩的反应.
主要方法:
- 开发一个高通量微流体平台,模拟人体毛细血管.
- 恶性和非恶性乳腺细胞系暴露于受控的收缩力.
- 对核完整性,细胞区域,炎症通路激活 (cGAS/STING,NF-κB,STAT,IRF3) 和基因表达的分析.
主要成果:
- 毛细管收缩诱导核膜破裂和细胞面积的短暂变化在两种细胞类型.
- 炎症通路 (cGAS/STING,NF-κB,STAT,IRF3) 暂时被激活,特别是在非恶性细胞中.
- 非恶性细胞显示出显著的转录变化,包括上皮细胞标记物下调,而转移性细胞的变化最小.
结论:
- 毛细血管中的机械力量可能会导致核损伤,并在正常和恶性细胞中引发炎症反应.
- 不同的细胞和转录反应表明,在转移过程中,机械力量可能会影响癌细胞的行为不同于正常细胞.
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