Effect of Acidic Tumor Microenvironment on Non‐Small‐Cell Lung Cancer Cells

In order to adapt to hypoxic stress, cancer cells switch from oxidative phosphorylation to aerobic glycolysis resulting in the metabolism of glucose to lactic acid. Increased lactic acid production and lack of removal of metabolic acids due to inefficient vasculature results in an acidic environment in the tumor parenchyma. Little is known about the effect of an acidic tumor environment on the motility of non‐ small cell lung cancer (NSCLC) cells. Our research focuses on the effect of acidic tumor microenvironment on motility and epithelial to mesenchymal transition (EMT) of NSCLC cell lines. NCI‐H1650 cells propagated in acidic pH media (pH ~ 6.5 to 6.7) showed a significant alteration in phenotype compared to the cells propagated in neutral pH media (pH ~ 7.2 to 7.4). Preliminary data on cell proliferation indicates that the acidic environment significantly decreased cell viability. No difference in motility was observed between H1650 cells propagated in acidic or neutral pH media. Expression of E‐ cadherin, an epithelial marker, was not affected by an acidic environment. Expression of vimentin, a mesenchymal marker, was observed at the mRNA level but no vimentin protein was observed, indicating altered translation, stability, or post translational modification of the protein. Examination of other EMT markers is in progress. These results indicate that unlike observations in AT‐1 prostate carcinoma cells [Pflugers Arch 466 (2014) 2127], changes in lung cancer cells by accumulation of acid in the tumor microenvironment results in modest promotion of metastatic potential.