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Blind mole rats may hold key to cancer

Rodents' cells commit mass suicide to stop tumours in their tracks.

The blind mole rat is the latest inductee to a special club: disease-resistant animals that might hold cellular clues to treating cancer in humans.

Cell cultures from two species of blind mole rat, Spalax judaei and Spalax golani, behave in ways that render them impervious to the growth of tumours, according to work by Vera Gorbunova at the University of Rochester in New York and her colleagues[1]. And the creatures seem to have evolved a different way of doing this from that observed in their better known and similarly cancer-resistant cousin, the naked mole rat (Heterocephalus glaber).

Some 23% of humans die of cancer, but blind mole rats — which can live for 21 years — seem to be immune to the disease.

“These animals are subject to terrific stresses underground: darkness, scarcity of food, immense numbers of pathogens and low oxygen levels. So they have evolved a range of mechanisms to cope with these difficulties,” explains co-author Eviatar Nevo, who has published papers on the animals since 1961. “I truly believe work with these animals will bring a dramatic revolution in medicine.”

Three years ago, Gorbunova was involved in another study describing the unusual way in which the cells of naked mole rats behave in the lab[2]. The authors say that this hints at how the rats resist cancer in the wild. When healthy cells from most animals are grown in cell culture, they divide until they form a single layer of cells covering the dish in which they are resident. At this point, healthy cells stop dividing, whereas cancerous ones continue to spread. But the healthy cells of naked mole rat cells behave as if they are 'claustrophobic', ceasing to divide much sooner than cells from other species.

“We thought the blind-mole-rat cells would use the same mechanism” as those of naked mole rats, says Gorbunova, “so the fact that they do not was a big surprise”. Rather than ceasing to divide, the cells of blind mole rats die en masse, in a bout of cell suicide that Gorbnova and her co-authors call “concerted cell death”.

This seems to be triggered by the collective release of a signalling molecule called interferon-beta, although what causes this is unclear. “The cells have some way of sensing when they are overproliferating, but we still don’t know precisely how they sense that,” Gorbnova says. “This is what we need to find out next, because it could provide some clue as to how we could activate the same process in human cells.”

Inadequate methods?

However, this is not necessarily the mechanism that allows blind mole rats to resist cancer, points out Jerry Shay at the University of Texas, who studies mechanisms of cellular ageing and death. “It is possible the researchers simply have not worked out adequate methods to maintain these cells long term in culture,” he says. “It’s possible that the culture conditions are causing increased stress on the cells, resulting in cell death.”

Indeed, no biologist has figured out how to keep blind mole rat cells cultures alive long-term in the lab. “If we apply the same technique that works for 20 other species of rodent, for some reason that’s not good enough for blind mole rat cells — they always die,” says Gorbunova.

But, counter-intuitively, mass cell death might be the very thing that makes the animals so long-lived: it could be a natural mechanism their bodies use to clear precancerous cells, stopping tumours in their tracks.

References

  1. 1

    Gorbunova, V. et al. Proc Natl Acad Sci USA. http://www.pnas.org/cgi/doi/10.1073/pnas.1217211109 (2012)

  2. 2

    Seluanov, A. et al. Proc Natl Acad Sci USA 106 19207–19208. (2009).

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Genome sequencing reveals insights into physiology and longevity of the naked mole rat 2011-Oct-12

Naked mole-rats don't feel the burn 2008-Jan-28

Old mole-rat boosts ageing research 2002-Nov-18

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Eviatar Nevo

Vera Gorbunova

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Cormier, Z. Blind mole rats may hold key to cancer. Nature (2012). https://doi.org/10.1038/nature.2012.11741

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