Underground rodents evolved a way to zap mutating tissue
Subterranean rodents with no eyes may show scientists a new way to beat cancer.
Blind mole rats — solitary, tunnel-dwelling cousins of rats and mice — live a long time and don’t get cancer. Biologists thought the animals probably avoided the disease through the same strategy seen in naked mole rats, another long-lived subterranean rodent related to guinea pigs. In those animals, a cell-death program turns on when cells get overcrowded, as might happen in a tumor.
But it turns out that blind mole rats have their own way of dealing with tumors, one that stems from adaptation to an underground lifestyle in which oxygen is scarce, researchers from New York and Israel report online November 5 in the Proceedings of the National Academy of Sciences.
The blind mole rats’ distinct way of avoiding cancer is surprising, says Steven Austad of the University of Texas Health Science Center in San Antonio. “This is like finding two needles in a haystack,” he says.
Blind mole rats ought to be more susceptible to cancer because their cells can’t kill themselves through a type of cell suicide called apoptosis. Low oxygen conditions, such as those common in blind mole rats’ burrows, usually cause cells to commit suicide. To survive underground, the blind rodents had to evolve a countermeasure, a mutation in a cancer-fighting protein called p53. That mutation prevents cells from undergoing apoptosis, a type of cell death in which cells dismantle themselves from the inside — and a process used to kill off cancer cells. Human cancer patients often have similar mutations, which prevent tumor cells from dying.
But blind mole rat cells find a way to off themselves. Growing cells in laboratory dishes, Vera Gorbunova of the University of Rochester in New York and colleagues found that the animals’ cells die on cue after three days. The cells release a chemical called interferon-beta, which the immune system normally uses to fight viruses. In this case, the chemical caused blind mole rat cells to burst open in a violent death known as necrosis.
The researchers are now trying to determine what triggers cells to release the chemical and how necrosis heads off tumors without damaging healthy tissues. That research will be important because necrosis is known to cause inflammation, which can also damage tissues, Austad says. Perhaps the animals kill off nascent cancer cells one at a time, heading off tumors while avoiding widespread inflammation, he says.
Adapting to low oxygen conditions may have inadvertently adapted mole rats, both blind and naked varieties, to avoid getting cancer, Austad says. But the fact that the two species do things differently “argues to me that there are probably many ways to prevent the out-of-control growth of cancer.”
V. Gorbunova et al. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. Proceedings of the National Academy of Sciences. Published online November 5, 2012. doi:10.1073/pnas.1217211109.