缺氧暴露史有助于根据细胞类型和原密度的未来细胞入侵
José A Almeida1,2, Diego B Avila1, Gregory D Longmore3,4
1Department of Biomedical Engineering, Washington University, St. Louis, United States.
Molecular biology of the cell
|May 6, 2025
概括
过去暴露于低氧 (低氧) 增加了癌细胞的入侵,即使在更密集的组织. 低氧原始细胞产生拉米宁332,增加粘附和侵入,这一过程被Cdh3耗尽所破坏.
科学领域:
- 癌症生物学 癌症生物学
- 瘤微环境的动力学
- 细胞机械生物学 细胞机械生物学
背景情况:
- 在癌症进展过程中,瘤微环境变得更加密集和缺氧.
- 细胞入侵受到矩阵密度和氧气水平的影响.
- 之前的氧气条件对未来细胞入侵的影响还不太清楚.
研究的目的:
- 研究过去的缺氧暴露如何影响不同原密度的癌细胞入侵.
- 阐明细胞入侵中缺氧诱导的变化背后的分子机制.
- 确定拉米宁332和Cdh3在低氧原料入侵中的作用.
主要方法:
- 在正常和低氧条件下培养正常的人类乳腺上皮细胞 (MCF10A) 和乳腺瘤细胞 (BT549).
- 评估不同原密度的细胞入侵率和原变形.
- 利用基因枯竭 (Cdh3) 和蛋白质分析 (laminin332) 来研究分子机制.
主要成果:
- 过去的缺氧暴露显著增加了细胞入侵和原变形,与正常缺氧对照相比.
- 低氧原料细胞显示强化入侵密集的原蛋白,与正常氧控制的细胞相反.
- 低氧原始的癌细胞产生了更多的拉米宁332,调解了细胞矩阵粘附和侵入的增加.
- 耗尽Cdh3取消了缺氧引起的侵袭和拉米宁332生产的增加.
结论:
- 癌细胞中的缺氧"记忆"增强了它们的入侵潜力,特别是在更密集的基质结构中.
- 通过Cdh3调节的拉米宁332的产生,是这种缺氧诱导的侵入性表型的关键媒介.
- 了解过去的氧气条件对于预测瘤入侵在不断发展的微环境中至关重要.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
02:53Adaptive Mechanisms in Cancer Cells
5.5K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.5K
01:24Overview of Cell-Matrix Interactions
6.9K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
6.9K