Hypoxia and the sodium hydrogen exchanger in non small cell lung cancer.

Abstract

The challenge of hypoxia in solid tumors induces several physiological changes in the cancer cell microenvironment including increased extracellular acidity. While proton exchangers including the sodium hydrogen exchanger (NHE1) support tumor cell invasion and metastasis, the relationship between hypoxia and increased acidity on migration/proliferation remains unclear. In this study we investigate the relationship between the sodium hydrogen exchanger isoform 1 (NHE1) and hypoxia inducible factor 1 (HIF‐1α) expression in H1299. HIF‐1α expression was observable after 24 hours of either 1% oxygen or chemically induced hypoxia and was maximally expressed after 72 hours of hypoxia. In parallel we found that NHE1 expression slightly increased after 72 hours in hypoxic conditions. We also show that hypoxia decreased cell proliferation in H1299 non small lung cancer cells. In addition, the impact of NHE1 inhibition on hypoxia induced MMP‐9 activity was altered. Hypoxia induced changes in cell motility and alkalization of intracellular pH was also observed. These results point to a relationship between hypoxia and NHE1 that influences cancer cell behavior. NIH Grant 1 R15 HL074924–01A1