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Could naked mole rats' "gooey" skin stop cancer?

A rodent that never gets cancer could hold the key to preventing or treating malignant tumours, BBC News reports

The story involves a curious creature called the naked mole rat that spends its life underground. Naked mole rats have been known to live for over 30 years – an exceptional lifespan for a rodent – and unlike other small rodents, scientists have never known one to get cancer.

Scientists who have studied the animal now think that a substance that may help to make it elastic enough to squeeze through underground tunnels, may also protect the animal against cancer. The supposedly “gooey”, or viscous, substance, called HMM-HA, is produced in the naked mole rat’s skin.

This is an intriguing story about a fascinating and arresting-looking creature. These findings are likely to spawn further research into HMM-HA to investigate its potential for cancer prevention. However, there is a very long way to go between lab experiments on rodents and the development of successful cancer prevention in humans.

Where did the story come from?

The study was carried out by researchers from the University of Rochester in New York, Tongji University in China and the University of Haifa in Israel. It was funded by the US National Institutes of Health and Ellison Medical Foundation. The study was published as a letter in the peer-reviewed journal, Nature.

It was covered fairly by the BBC and The Daily Telegraph.

What kind of research was this?

The research involved a number of laboratory and animal experiments to find out why the naked mole rat (Heterocephalus glaber) seems not to develop cancer.

Researchers point out that the naked mole rat displays “exceptional longevity”, with a maximum lifespan of over 30 years. This is the longest lifespan reported for any rodent species and is especially striking considering its small size. In comparison, a similarly sized mouse lives only up to four years. Naked mole rats also show an unusual resistance to cancer, with no cases of the disease detected in observational studies of large colonies of these animals.

Previous studies have identified a possible anti-cancer mechanism in mole rats, involving a process that stops cell growth when cells come into contact with each other or the molecules secreted around the cells that give them structural support (called the extracellular matrix). However, scientists remained puzzled as to exactly what might trigger this process.

What did the research involve?

The researchers grew a type of connective tissue cells called fibroblasts in the laboratory. They noticed that the solution they were being grown in (the culture medium) became very viscous (sticky) after a few days. They identified the sticky substance being secreted by the mole rat cells as a large carbohydrate molecule called high molecular mass hyaluronic acid (HMM-HA). 

Along with other chemicals, HA forms part of the extracellular matrix (or framework) that gives tissues their shape and makes skin elastic. HA molecules can vary in their length, and their effects on cells differ depending on their length. The HMM-HA molecules are very long, and are known to suppress signals telling cells to divide.

They carried out several laboratory experiments to analyse the HMM-HA and to compare the HA produced in naked mole rat tissue to HA found in other rodents and in humans. Further experiments aimed to find out if the HMM-HA might act as the trigger for the mole rats’ anti-cancer mechanism, to prevent cancer cells replicating.

One experiment involved blocking the gene that encodes the enzyme that makes HA to see how mole rat cells would be affected. These cells were implanted into mice to see whether they would turn cancerous.

What were the basic results?

Their experiments had several results, finding that:

  • HA is secreted in the tissues of naked mole rats in large amounts compared to the amount found in mouse and guinea pig tissues.
  • Naked mole rat cells secrete HA molecules that are exceptionally long and therefore heavier than shorter HA molecules, which is why it is called “high molecular mass” HA. Mice, guinea pig and human HAs are shorter.
  • The gene that encodes the enzyme that makes HA has differences to the same gene in other mammals, and introducing this gene into human cells in the laboratory resulted in them producing HMM-HA.
  • Activity of the enzymes that break down HA (called HAases) is far lower in naked mole rats than in human, mouse or guinea pig cells.

In their experiments looking at whether HMM-HA could be responsible for the cancer-resistance seen in naked mole rats they found that:

  • If mole rat cells HMM-HAs were broken down by adding HAase, they no longer stopped growing when they came into contact with other cells or the extracellular matrix.
  • Blocking the gene that encodes the enzyme that makes HA makes naked mole rat cells susceptible to becoming cancerous forming tumours in mice.

How did the researchers interpret the results?

The researchers think that naked mole rats have evolved a high concentration of HMM-HA in the skin to provide the skin flexibility needed for life underground. This trait, they say, has a key role in protecting them against cancer. They suggest that their findings open “new avenues for cancer prevention and life extension”.

Conclusion

This is a fascinating study that suggests that a carbohydrate molecule called HMM-HA found in high concentrations in the skin of naked mole rats also has a role in protecting them against cancer. It is possible that the presence of HMM-HA may be only one of several factors involved in preventing cancer in this rodent.

Although this molecule appears to contribute to the cancer resistance of the naked mole rat, whether this can be translated into successful ways of preventing cancer or extending life in humans remains to be seen. A lot of fascinating research remains to be done.

 

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