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

Studies have suggested that cancerous tissue has a lower ¹⁵N/¹⁴N 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 ¹⁵N/¹⁴N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, ¹⁵N/¹⁴N was negatively correlated with tumor cell density. The magnitude of ¹⁵N 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 ¹⁵N 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 ¹⁵N/¹⁴N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.