Nitrogen isotopic composition as a gauge of tumor cell anabolism-to-catabolism ratio

Studies have suggested that cancerous tissue has a lower (15)N/(14)N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the (15)N/(14)N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, (15)N/(14)N was negatively correlated with tumor cell density. The magnitude of (15)N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations in the anabolism-to-catabolism ratio. However, tumor (15)N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support (15)N/(14)N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.