Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6242, New Zealand.
School of Medical Science, Griffith University, Southport, QLD 4222, Australia.
Cell Metab. 2015 Jan 6;21(1):81-94. doi: 10.1016/j.cmet.2014.12.003.
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.
我们报告称，没有线粒体 DNA（mtDNA）的肿瘤细胞表现出肿瘤生长延迟，并且肿瘤的形成与从宿主细胞中获得 mtDNA 有关。这导致了源自缺乏 mtDNA 的原发性肿瘤的细胞中，线粒体功能部分恢复，并且肿瘤生长的潜伏期缩短。来自循环肿瘤细胞的细胞系显示出线粒体呼吸功能的进一步恢复和肿瘤生长的中间潜伏期，而来自肺转移的细胞则完全恢复了呼吸功能，并且肿瘤生长没有潜伏期。线粒体呼吸（超级）复合物的逐步组装与获得呼吸功能相关。我们的研究结果表明，线粒体 DNA 从肿瘤微环境中的宿主细胞向呼吸功能受损的肿瘤细胞的水平转移，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，并支持恶性细胞高可塑性的观点。
