Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary.
School of Ph.D. Studies, Semmelweis University, Budapest, 1085, Hungary.
Sci Rep. 2024 Sep 3;14(1):20482. doi: 10.1038/s41598-024-70769-w.
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.
肺癌是全球癌症相关死亡的主要原因。转移是导致死亡的最常见原因，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性的影响在很大程度上仍未得到探索，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缺氧条件下单细胞迁移和侵袭中的细胞增殖和迁移活性的变化。还分析了与细胞对缺氧反应、上皮-间充质转化、增殖和细胞凋亡相关的关键基因和蛋白的变化。一般来说，我们观察到缺氧条件下细胞增殖没有变化，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，划痕试验中在细胞汇合条件下的侵袭能力在缺氧条件下增强，而单细胞迁移能力普遍降低。此外，我们检测到 EMT 标志物表达的变化，这与缺氧对迁移和转移促进作用的增强一致。总之，我们的研究表明，缺氧对细胞增殖、迁移和基因表达的影响具有细胞系、暴露时间和迁移类型依赖性。我们的研究结果有助于更好地理解和应对癌症转移。
