使用各种体外肺腺癌模型,缺氧对运动的不同影响。
Differential effects of hypoxia on motility using various in vitro models of lung adenocarcinoma.
发表日期:2024 Sep 03
作者:
Sára Eszter Surguta, Marcell Baranyi, Laura Svajda, Mihály Cserepes, Ivan Ranđelović, Enikő Tátrai, Balázs Hegedűs, József Tóvári
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
肺癌是全球癌症相关死亡的主要原因。转移是最常见的死亡原因,其中缺氧被认为起着关键作用。然而,缺氧对癌细胞转移潜力和迁移活动的影响在很大程度上尚未被探索,需要进行详细的科学研究。因此,我们分析了肺腺癌细胞系在常氧和低氧条件下单细胞迁移和侵袭的细胞增殖和迁移活性的变化。还分析了与细胞对缺氧、上皮间质转化、增殖和凋亡的反应相关的关键基因和蛋白质的变化。一般来说,我们观察到缺氧条件下增殖没有变化,也没有检测到细胞凋亡的诱导。有趣的是,我们观察到,在大多数细胞系中,单细胞运动普遍降低,而汇合条件下使用划痕实验的侵袭则因缺氧而增强。此外,我们检测到 EMT 标志物表达的变化,这与缺氧增强的运动性和促进转移作用一致。总之,我们的研究表明缺氧对细胞增殖、运动和基因表达的细胞系、暴露时间和迁移类型依赖性影响。我们的结果有助于更好地理解和应对癌症转移。© 2024。作者。
Lung cancer is the leading cause of cancer-related death globally. Metastasis is the most common reason of mortality in which hypoxia is suggested to have a pivotal role. However, the effect of hypoxia on the metastatic potential and migratory activity of cancer cells is largely unexplored and warrants detailed scientific investigations. Accordingly, we analyzed changes on cell proliferation and migratory activity both in single-cell migration and invasion under normoxic and hypoxic conditions in lung adenocarcinoma cell lines. Alterations in crucial genes and proteins associated with cellular response to hypoxia, epithelial-mesenchymal transition, proliferation and apoptosis were also analyzed. Generally, we observed no change in proliferation upon hypoxic conditions and no detectable induction of apoptosis. Interestingly, we observed that single-cell motility was generally reduced while invasion under confluent conditions using scratch assay was enhanced by hypoxia in most of the cell lines. Furthermore, we detected changes in the expression of EMT markers that are consistent with enhanced motility and metastasis-promoting effect of hypoxia. In summary, our study indicated cell line-, time of exposure- and migrational type-dependent effects of hypoxia in cellular proliferation, motility and gene expression. Our results contribute to better understanding and tackling cancer metastasis.© 2024. The Author(s).