美国南阿拉巴马大学Simon Grelet小组研制了肿瘤转移过程中线粒体的神经癌转移。相关论文于2025年6月25日发表于国际顶尖学术期刊《自然》杂志上。

在这里，该课题组人员发现癌症相关神经元通过将线粒体转移到癌细胞来增强癌症代谢可塑性。乳腺癌去神经支配和神经-肿瘤共培养模型证实，神经元显著改善肿瘤的能量学。与癌细胞共培养的神经元进行代谢重编程，导致线粒体质量增加并随后将线粒体转移到邻近的癌细胞。为了精确地追踪受体细胞的命运，课题组人员开发了MitoTRACER，这是一种细胞间线粒体转移的报告器，可以永久地标记受体癌细胞及其后代。在原发肿瘤中获得神经元线粒体的癌细胞的谱系追踪和命运定位揭示了它们在扩散后转移部位的选择性富集。总的来说，他们的数据强调了原发性肿瘤中接受神经元线粒体的癌细胞的转移能力增强，为神经系统如何支持癌症代谢和转移传播提供了新的思路。

据了解，神经系统在癌症生物学中具有关键作用，病理研究已将瘤内神经密度与转移联系起来。然而，癌症相关神经元的确切影响和神经-癌症界面的通讯通道仍然知之甚少。先前的啮齿动物和人类癌症去神经支配模型强调了癌症对神经的依赖，但驱动神经介导的癌症侵袭的潜在机制仍然未知。

附：英文原文

Title: Nerve-to-cancer transfer of mitochondria during cancer metastasis

Author: Hoover, Gregory, Gilbert, Shila, Curley, Olivia, Obellianne, Clmence, Lin, Mike T., Hixson, William, Pierce, Terry W., Andrews, Joel F., Alexeyev, Mikhail F., Ding, Yi, Bu, Ping, Behbod, Fariba, Medina, Daniel, Chang, Jeffrey T., Ayala, Gustavo, Grelet, Simon

Issue&Volume: 2025-06-25

Abstract: The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. Neurons cocultured with cancer cells undergo metabolic reprogramming, resulting in increased mitochondrial mass and subsequent transfer of mitochondria to adjacent cancer cells. To precisely track the fate of recipient cells, we developed MitoTRACER, a reporter of cell-to-cell mitochondrial transfer that permanently labels recipient cancer cells and their progeny. Lineage tracing and fate mapping of cancer cells acquiring neuronal mitochondria in primary tumours revealed their selective enrichment at metastatic sites following dissemination. Collectively, our data highlight the enhanced metastatic capabilities of cancer cells that receive mitochondria from neurons in primary tumours, shedding new light on how the nervous system supports cancer metabolism and metastatic dissemination.

DOI: 10.1038/s41586-025-09176-8

Source: https://www.nature.com/articles/s41586-025-09176-8