Cancer-proof rodents could have clues to tumour prevention

Naked mole rat
One important message we would like to convey to the cancer research community is that it is important to study naturally cancer-proof animals, as novel mechanisms can be discovered that could then be ‘imported’ into other species.
Professor Vera Gorbunova
Biologists in the United States are hopeful that identification of the substance that cancer-proofs naked mole rats could advance cancer prevention and treatment in humans…

Scientists from the Department of Biology at the University of Rochester have discovered the reason behind a hairless subterranean rodent’s resistance to cancer. The findings are published in the journal Nature this week.

The group of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, began their investigation after noticing that a gooey substance from cultures of naked mole rat cells were clogging vacuum pumps and tubing. It was also observed that cultures of mole rat cells possessed a viscosity lacking in media containing human, mouse and guinea pig cells. 

"The naked mole rat (Heterocephalus glaber) is the longest-lived rodent, living on average 10 times longer than a similar-sized mouse," Professor Gorbunova told ScienceOmega.com. "Even more surprisingly, the naked mole rat is cancer-proof. We were fascinated to learn how naked mole rats can remain cancer-proof and whether this can be applied to benefit human health."

Understanding the goo
 

The scientists identified the substance as high molecular weight hyaluronan (HMW-HA), a chemical which is by no means unique to the naked mole rat.

"HMW-HA is present in all mammals, said Professor Gorbunova. "However, in the naked mole rat it has a very high molecular weight; naked mole rat HA is six or more times longer than human HA."

The average human has around 15 grams of HA in their body at any given time, and HMW-HA is already used in humans to relieve pain in the knees of arthritis patients and in anti-wrinkle injections. The team decided to test the role of HMW-HA in the cancer-proofing of these small rodents, and were able to confirm that its removal made them vulnerable to tumour growth as Professor Gorbunova explained.

"When we prevented the cells from making HMW-HA, or sped up its degradation, naked mole rat cells became susceptible to malignant transformation."

In addition, the researchers were able to pinpoint the gene responsible for the production of HMW-HA – HAS2 – and found that it differed in naked mole rats as compared to all other animals. Furthermore, HMW-HA turnover in Heterocephalus is much slower than in other organisms, resulting in an accumulation of the substance in their tissues. Experts hypothesise that high HA levels in their skin has helped mole rats to adapt to life in underground tunnels.

‘Novel mechanisms can be discovered’
 

While much oncology research focuses on animals that a susceptible to cancer, Professor Gorbunova and her colleagues argue that cancer studies could learn a lot from naked mole rats and animals like them.

"One important message we would like to convey to the cancer research community is that it is important to study naturally cancer-proof animals, as novel mechanisms can be discovered that could then be ‘imported’ into other species," she commented.

The current paper follows on from previous research in which Professors Gorbunova and Seluanov demonstrated that the p16 gene halts proliferation of cells crowding too close together in the naked mole rat. They have now shown that HMW-HA is responsible for activation of the p16 gene. The hope, if further tests are successful, is that an anti-cancer response could eventually be produced in humans.

"We are currently testing whether increasing HMW-HA in mice will reduce the incidence of cancer," Professor Gorbunova related. "We are also interested in looking at other cancer-resistant species to understand what novel mechanisms have evolved there."

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