N isotopes in Mice Models

 

Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), we hypothesize that its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. If true, the distinct 15N/14N signature of cancer tissue could be used as a new diagnostic tool. We are currently investigating this hypothesis by measuring the isotopic composition of healthy and cancerous tissue in mice micro-biopsies with a novel highly sensitive technique.

Mice brain and head&neck tumor microbiopsies

In a recent study we analyzed micro-biopsies of murine tumors and adjacent tissues for 15N/14N using novel high-sensitivity methods (Straub et al. 2021). The isotopic analysis was pursued in mice models with mature orthotopic brain and head&neck tumors generated by implantation. In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. Although much more work in mice and human models is needed, our findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

Screen Shot 2021-07-13 at 17.46.03.png

N isotopic composition of tumor, tumor bed and healthy tissue in samples from brain tumor-bearing mice