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Cancer immunity of strange underground rat revealed

Don’t go by looks. Smithsonian's National Zoo

Researchers have discovered how one of the world’s oddest mammals developed resistance to cancer, and there is hope that their work could help fight the disease in humans.

Naked mole rats live underground, where environmental conditions are harsh but predators are few. They can live for more than 30 years, almost seven times longer than its close cousin the house mouse, which is particularly susceptible to cancer. They breathe slowly due to the limited supply of oxygen, survive on very little food, have poor sight and are largely indifferent to pain.

They are also the only mammals that do not regulate their body temperature. Because they live in colonies where the queen rat does the job of producing progeny and only a few males father the litters, their sperms become lazy.

For cancer researchers, mice and naked mole rats fall on two extremes of the disease spectrum. Mice are used as animal models of disease because of their short lives and high incidence of cancer. These help researchers study the mechanism of cancer occurrence and test drugs that fight the disease.

Naked mole rats, on the other hand, have never developed cancer in the years that they have been studied. In labs, researchers often don’t wait for their animal models to develop cancer. Instead they induce cancer by blasting the animals with gamma radiation, transplanting tumours or injecting cancer-causing agents. Do that to a naked mole rat, though, and nothing happens.

Now, Vera Gorbunova and Andrei Seluanov at the University of Rochester think that they may have found one mechanism by which naked mole rats defend themselves against cancer. Their results, reported today in the journal Nature, make for a strange tale.

While studying cells taken from the armpits and lungs of naked mole rats, they found an unusually thick chemical surrounding the cells. This turned out to be hyaluronan, a substance that is present in all animals, where its main job is to hold cells together. Beyond providing mechanical strength, it is also involved in controlling when cells grow in number.

Cancer relies on the unregulated growth of cells, so hyaluronan was thought to be involved in the progression of malignant tumours. According to Gorbunova, there are aspects of hyaluronan may regulate cell growth: as well as its amount and thickness. As a polymer, the greater the number of hyaluronan molecules in a single chain the thicker it becomes.

When the molecular mass is high, cells are “told” to stop increasing in number. When the molecular mass is low, they are “asked” to proliferate. In the case of the naked mole rat, Gorbunova found that the molecular mass was unusually high, as much as five times that of mice or humans.

To understand whether this unusual hyaluronan was responsible for cancer resistance in naked mole rats, Gorbunova increased the amount of enzyme that degrades the chemical, reducing its molecular weight. Soon after, she observed that the rat’s cells readily started growing in thick clusters, like cancerous mouse cells do.

In a separate experiment, she also tested this hypothesis by reducing the amount of hyaluronan by knocking out the genes that encode for its production. Then on injecting cancer-causing virus, instead of resisting, the naked mole rat’s cells became cancerous.

Gorbunova thinks that having thick hyaluronan might have helped increase the elasticity of the rat’s skin, allowing it to live in small tunnels underground. This trait might then have accidentally developed a new role of preventing cancer.

Rochelle Buffenstein, a physiologist at the University of Texas Health Science Center, who has studied naked mole rats for years was pleased to see that some light has been shed on this creature’s remarkable resistance to cancer. “As we learn more about these cancer-resistant mechanisms that are effective and can be directly pertinent to humans, we may find new cancer prevention strategies,” she said.

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