Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, 1007 Lausanne, Switzerland.
Max Planck Institute for Chemistry, 55128, Mainz, Germany.
BMC Cancer. 2021 Jul 13;21(1):805. doi: 10.1186/s12885-021-08489-x.
Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (N/N), its recycling may cause cancer tissue to have lower N/N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their N/N.
Micro-biopsies of murine tumors and adjacent tissues were analyzed for N/N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively.
In the 7 mice analyzed, the brain tumors had distinctly lower N/N 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 N/N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question.
The findings, coupled with the high sensitivity of the N/N 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.
癌细胞可以回收代谢产生的铵以供生长。由于这种铵的氮同位素比值（N/N）较低，其回收可能导致肿瘤组织的 N/N 比周围健康组织低。我们研究了在个体小鼠的特定组织类型中，是否可以根据其 N/N 区分肿瘤组织和健康组织。
使用新的高灵敏度方法分析了小鼠肿瘤和相邻组织的 N/N。在 Nude 和 C57BL/6 小鼠模型中进行了同位素分析，这些模型分别通过植入 H454 和 MEERL95 小鼠细胞生成了成熟的原位脑肿瘤和头颈部肿瘤。
在分析的 7 只小鼠中，脑肿瘤的 N/N 明显低于健康的神经组织。在 5 只患有头颈部肿瘤的小鼠中，差异较小且更具变异性。这至少部分是由于肿瘤细胞浸润了健康的头颈部组织。然而，这也可能表明肿瘤组织和健康组织之间的 N/N 差异取决于所研究的健康器官的氮代谢。
这些发现，加上这里使用的 N/N 测量方法的高灵敏度，为基于微创活检的恶性肿瘤诊断提供了一种新方法，也为癌症代谢的研究提供了一种途径。
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