线粒体基因组采集可在没有线粒体 DNA 的情况下恢复癌细胞的呼吸功能和致瘤潜能
Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA
Keywords：tumor cells、mitochondrial function、complex II
关键词：肿瘤细胞、线粒体功能、复合体II
作者：Tan AS, Baty JW, Dong L, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Pesdar EA, Sobol M, Filimonenko A, Stuart S, Vondrusova M, Kluckova K, Sachaphibulkij K, Rohlena J, Hozak P, Truksa J, Eccles D, Haupt LM, Griffiths LR, Neuzil J, Berridge MV
出版期刊：《Cell Metabolism》（2015/1/6）
Abstract：
We report that tumor cells without mitochondrial DNA (mtDNA) show delayed tumor growth, and that tumor formation is associated with acquisition of mtDNA from host cells. This leads to partial recovery of mitochondrial function in cells derived from primary tumors grown from cells without mtDNA and a shorter lag in tumor growth. Cell lines from circulating tumor cells showed further recovery of mitochondrial respiration and an intermediate lag to tumor growth, while cells from lung metastases exhibited full restoration of respiratory function and no lag in tumor growth. Stepwise assembly of mitochondrial respiratory (super)complexes was correlated with acquisition of respiratory function. Our findings indicate horizontal transfer of mtDNA from host cells in the tumor microenvironment to tumor cells with compromised respiratory function to re-establish respiration and tumor-initiating efficacy. These results suggest pathophysiological processes for overcoming mtDNA damage and support the notion of high plasticity of malignant cells.4T1ρ0 cells are a kind of mt gene-deficient cells. These cells cannot form tumors due to the loss of cell function due to gene defects in mice. Their energy metabolism is shown in the figure, which is completely different from normal cancer cells 4T1 (Par). 4T1 (Par) cells can produce corresponding energy metabolism curve changes according to the addition of different reagents, but 4T1ρ0 cells have no change; 4T1ρ0 cells are injected into mice to form 4T1ρ0SC cells, which can form 4T1ρ0CTC circulating tumor cells in the blood over time, and 4T1ρ0SCL lung metastatic tumor cells; energy metabolism measurement results show that with the increase of tumor cells in vivo, the tumor microenvironment can induce 4T1ρ0SC mt gene-deficient mouse breast cancer cells to gradually restore mitochondrial function, and in 4T1ρ0SCL lung metastatic tumor cells During the measurement of energy metabolism, it was found that the recovery of mitochondrial function was correlated with the function of complex II (CII) on the inner mitochondrial membrane; the experiment combined the physical observation of tumor formation in living animals, and it was found that the recovery of mitochondrial function was associated with tumor formation. have a certain correlation.
文章摘要：
我们报告说，没有线粒体 DNA (mtDNA) 的肿瘤细胞显示出肿瘤生长延迟，并且肿瘤形成与从宿主细胞中获取 mtDNA 相关。这导致源自原发性肿瘤的细胞的线粒体功能部分恢复，这些原发性肿瘤由没有 mtDNA 的细胞生长而成，并且肿瘤生长的延迟更短。来自循环肿瘤细胞的细胞系表现出线粒体呼吸的进一步恢复和肿瘤生长的中间滞后，而来自肺转移瘤的细胞表现出呼吸功能的完全恢复并且肿瘤生长没有滞后。线粒体呼吸（超）复合物的逐步组装与呼吸功能的获得相关。我们的研究结果表明，mtDNA 从肿瘤微环境中的宿主细胞水平转移到呼吸功能受损的肿瘤细胞，以重新建立呼吸和肿瘤起始功效。这些结果表明了克服 mtDNA 损伤的病理生理过程，并支持恶性细胞的高可塑性概念。4T1ρ0细胞是一种mt基因缺陷型细胞，该细胞在小鼠体内因基因缺陷导致细胞功能缺失而无法形成肿瘤，其与正常癌细胞 4T1（Par）效果完全不同，4T1（Par）细胞可根据添加不同试剂产生相应的能量代谢曲线变化，4T1ρ0细胞则没有任何变化；4T1ρ0细胞注入小鼠体内形成4T1ρ0SC细胞，随时间延长，可形成血液中的4T1ρ0CTC 循环肿瘤细胞、以及4T1ρ0SCL 肺转移肿瘤细胞；能量代谢测量结果可见，随肿瘤细胞在生物体内的时间增长，肿瘤微环境可诱导4T1ρ0SC mt基因缺陷型小鼠乳腺癌细胞逐步恢复线粒体功能，并且在对4T1ρ0SCL 肺转移肿瘤细胞的能量代谢测量过程中发现，线粒体功能的恢复与线粒体内膜上的复合体II（CII）的功能具有相关性；实验结合了活体动物肿瘤形成物理观察，结果发现，线粒体功能的恢复与肿瘤形成具有一定的相关性。
文章题目、关键词与摘要译文仅用于参考。
