(Open access funding provided by Semmelweis University)
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.
