Monday, November 5, 2012

They May Not Win Any Beauty Contests, But They Both Won The Biological Lottery

What do naked mole rats and blind mole rats have in common?

Besides two-thirds of their name, that is- and the fact that you probably wouldn't want to find yourself next to a representative of either species in a dark underground tunnel.

A face only a mother could love. No, that's not an undercooked sausage, that's a naked mole rat. Image credit: Meghan Murphy, Smithsonian's National Zoo/File
Ditto: blind mole rat. Image credit: University of Rochester
The answer, surprisingly, is that as far as we know both species are resistant to cancer, the biological scourge of many complex multicellular organisms.

But the similarities end there. Even though the rodents are two peas in a loosely related evolutionary pod, the way in which cancer resistance is conferred differs between naked and blind mole rats.

Three years ago a team of researchers led by Vera Gorbunova at the University of Rochester linked naked mole rats' ability to evade the development of cancerous cells to the rodents' p16 gene. One of the hallmarks of cancerous tumors is that cancerous cells tend to literally overstep the cellular boundaries between themselves and their neighbors. When a normal cell bumps up against neighboring cells, that serves as its cue to cease any additional divisions in a phenomenon known as contact inhibition. Many cancerous cells, however, continue dividing regardless of the crowding in their immediate environment.

Mammalian cells will only tolerate so much crowding before reaching levels sufficient to activate contact inhibition. In naked mole rats, however, the cellular crowding tolerance level is much, much lower. Even at low-level crowding conditions the researchers found that the gene p16 was activated in the tunnel-dwelling rodents, stemming the overproliferation of cells earlier than in their murine (mouse) counterparts.

Since then Gorbunova and her team have extended their study to include blind mole rats, who seem to remain cancer-free along with their hairless, wrinkled cousins. Interestingly, they found that a second mechanism seems to be responsible for the blind mole rats' cancer resistance. After taking the rodent's cells and forcing them to divide beyond normal limits in a cell culture dish, they found that after 15-20 divisions all of the cells quickly died off. The mass cell suicide, they found, is triggered by a protein known as interferon beta which is secreted from the precancerous cells. In addition to committing 'cellular suicide' by being toxic to the original secreting cell, interferon beta also killed off other neighboring cells. The 'clean sweep' therefore eliminates both the precancerous cells and other potentially precancerous cells as a preventative measure.

Any increased understanding of the mechanisms by which cancer can develop or ways in which it can be combated are valuable tools in our medical arsenal in the fight against cancer, which is currently the second most common cause of death in the US. Despite their somewhat frightening appearance, these underground rodents are invaluable resources as models for the study of cancer mechanisms and natural defenses against cancer. They may not win be winning any beauty contests, but these tunnel-dwelling critters may be a beautiful opportunity for the advancement of the current state of cancer research.

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