Non-overlap of tumor acidosis and hypoxia: new rationale to target fatty acid desaturase activity in cancer.
A population of cancer cells located in the acidic tumor compartment were shown to exhibit an aggressive phenotype making it very attractive to target them. In this study, an unbiased strategy was used to isolate acidic, non-hypoxic cancer cells from hypoxic (acidic) and non-acidic (non-hypoxic) ones. We used a combination of carbonic anhydrase CA9 antibodies as a marker of acidosis regardless of the pO2 environment and HRE-GFP reporter as a hypoxia marker to isolate distinct cell populations from 3D tumor spheroids. Transcriptomic analysis of sorted CA9-positive but hypoxia-negative cancer cells led us to identify fatty acid (FA) desaturase activity as an enriched pathway in these cells. Overall design: In this study, an unbiased strategy was used to isolate acidic, non-hypoxic cancer cells from hypoxic (acidic) and non-acidic (non-hypoxic) ones. We used a combination of carbonic anhydrase CA9 antibodies as a marker of acidosis regardless of the pO2 environment and HRE-GFP reporter as a hypoxia marker to isolate (by FACS) distinct cell populations from 3D tumor spheroids.