Most cancer deaths occur when cells in a primary tumor metastasize, yet the mechanisms by which tumor cells acquire metastatic properties remain poorly understood. Ishikawa et al. explored the role of mitochondria in this process by taking mouse tumor cell lines with either a high or low propensity to metastasize and swapping their mitochondrial DNA (mtDNA). Interestingly, the recipient cells acquired the metastatic potential of the cells donating the mtDNA. In one tumor cell line examined in detail, the mtDNA conferring high metastatic potential was found to harbor mutations that led to overproduction of reactive oxygen species (ROS), and up-regulation of nuclear genes involved in metastasis. Pretreatment of tumor cells with ROS scavengers reduced their ability to metastasize in mouse models, suggesting a possible avenue for the development of therapies to suppress metastasis.
K. Ishikawa, K. Takenaga, M. Akimoto, N. Koshikawa, A. Yamaguchi, H. Imanishi, K. Nakada, Y. Honma, J.-I. Hayashi, ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320, 661-664 (2008). [Abstract] [Full Text]