PhD Scientific Days 2024

Poster Session Q - Pathological and Oncological Sciences 2.

Differential effects of hypoxia on the motility of lung adenocarcinoma cell lines

Text of the abstract

Introduction: Metastasis formation is a common cause of mortality in lung cancer patients, and it is hypothesized that hypoxia plays a key role in this process. However, the impact of hypoxia on the metastatic potential and migratory activity of cancer cells is largely unexplored and requires detailed investigations.
Material and methods: In our study, we included lung adenocarcinoma cell lines carrying different mutations of the growth factor pathway (H1975: EGFR T790M, PF901: BRAF V600E, PF139: KRAS G12C mutant, and H838: triple WT). We analyzed the changes in cell proliferation and migration activity under normoxic and hypoxic (1% O2) conditions in both single-cell and collective migration using scratch assay and video microscopy experiments. We also examined changes in key genes and proteins related to the hypoxic response, epithelial-mesenchymal transition, proliferation, and apoptosis using Western Blot and qPCR techniques.
Results: Chronic hypoxia proved to be an acute stressor for the cells. Generally, reduced proliferation was observed under hypoxic conditions without detectable induction of apoptosis. Interestingly, we observed that single-cell motility was generally reduced, while collective migration was increased in most cell lines under hypoxia. Additionally, changes were noted in the expression of EMT markers, consistent with the enhanced motility and metastasis-promoting effects of hypoxia.
Conclusion: In summary, our study suggests that the effects of hypoxia on proliferation, motility, and gene expression were cell line-, exposure time-, and migration type-dependent. Our findings contribute to a better understanding and potential treatment of metastasis.
Funding: The authors acknowledge financial support from the National Laboratories Excellence program [under the National Tumor Biology Laboratory Project (NLP-17, 2022-2.1.1-NL-2022-00010] and the Hungarian Thematic Excellence Program [TKP2021-EGA-44]. Project no. 1018567 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the KDP-2020 funding scheme.