Cancer often strikes its final, fatal blow when a tumor spreads to other organs. A new study published online today in Science sheds light on this poorly understood process, called metastasis. The researchers report that mutations in mitochondrial DNA can spur metastasis and that it can be reversed with drugs, at least in mice.
Mitochondria are the tiny organelles inherited from your mom that serve as the cell's powerhouses. They have their own DNA, called mtDNA. Ten years ago, cancer researchers noticed that mtDNA in tumor cells tends to be riddled with mutations--far more than in normal tissues. (This is in part because mtDNA is not packaged in proteins, which makes it more vulnerable to damage.) Some researchers think mtDNA may cause tumors. But others suggest that the mutations are simply a byproduct of the cancer; they note that people with mitochondrial diseases are not particularly cancer-prone, and cancer risk is not inherited maternally, as would be expected for a disease linked to mitochondria.
To explore the role of mtDNA mutations in cancer, Jun-Ichi Hayashi's group at the University of Tsukuba in Japan and collaborators swapped the mtDNA of two types of mouse tumor cells: one that tends to metastasize and another that does not. When they injected these hybrid cells under the skin of mice, the cells grew into tumors that eventually spread to the lungs. Mice that received the mtDNA from metastasizing cells had many more lung tumors than mice that had mtDNA from less metastasis-prone cells, suggesting that mtDNA was indeed the culprit. However, mtDNA did not seem to be involved in primary tumor formation: When the group swapped mtDNA from metastatic cells into normal cells, it did not cause these to form tumors.
The metastatic mtDNA appeared to do its dirty business thanks to two mutations that caused the mitochondria to overproduce so-called reactive oxygen species, which are toxic, DNA-damaging molecules. When the researchers put a drug that sops up these molecules into the drinking water of mice that had been given metastatic cells under the skin, they developed almost no lung tumors.
The paper is "a technical tour de force," says mitochondria researcher Robert Taylor of Newcastle University in the U.K., and the fact that antioxidants suppressed metastasis warrants further study, he says. Kornelia Polyak of the Dana-Farber Cancer Institute in Boston cautions, however, that clinical trials testing antioxidants to prevent cancer have yielded mixed results and that giving antioxidants to someone on chemotherapy could interfere with the treatment.