Secret of naked mole-rats immunity to cancer could help prevent disease in humans

Previous studies had concluded the animals almost never developed the disease – with only a handful of cases ever observed in the species – because their healthy cells were simply immune from becoming cancer cells.

A surprising new discovery about a hairless and wrinkly subterranean rodent could open the door to ways of preventing cancer in people, scientists have said.

The naked mole-rat, a virtually blind burrowing rodent native to east Africa, has long fascinated researchers due to its range of peculiar powers.

The large-toothed, tiny-eyed and cold-blooded creature is immune to certain types of pain, can survive for 18 minutes without oxygen, and can live for more than 30 years while defying the biological laws of ageing.

The mole-rat is also highly resistant to cancer, a trait which has made it focus of research teams studying the disease across the world.

However, researchers at the University of Cambridge have now shown for the first time that genes known to cause cancer in the cells of other rodents can turn mole-rat cells cancerous.

Instead, the team concluded, what sets the creature apart is a complex system of cells and molecules surrounding a cell, including the immune system.

The researchers believe interactions with this system, known as a microenvironment, stop initial stages of cancer from developing into tumours.

Dr Walid Khaled, a Cambridge pharmacologist and one of the senior authors of the study, said: “The results were a surprise to us and have completely transformed our understanding of cancer resistance in naked mole-rats.

“If we can understand what’s special about these animals’ immune systems and how they protect them from cancer, we may be able to develop interventions to prevent the disease in people”.

In the study, published in the journal Nature, the researchers analysed 79 different cell lines grown from intestine, kidney, pancreas, lung and skin tissue taken from 11 individual mole-rats. They infected cells with modified viruses to introduce genes known to cause cancer in mice and rat cells, but which were not expected to be able to turn mole-rat cells cancerous

“To our surprise, the infected naked mole-rat cells began to multiply and rapidly form colonies in the lab. We knew from this accelerated growth that they had become cancerous,” said Fazal Hadi, a postdoctoral research fellow and lead researcher in the study.

The team then injected these cells into mice, which within weeks formed tumours, a result which the researchers say indicates it is the environment of the mole-rat’s body that prevents cancer from developing.

This finding contradicts previous research, including a 2013 study which concluded mole-rat cells had evolved an inherent trait which stopped them turning cancerous in the first place.

However, the authors of the earlier study hit back at the Cambridge team. In a response published in Nature, the researchers – based mostly at New York’s University of Rochester – argued the new study achieved different results because it exposed the mole-cat cells to “artificially high” levels of cancer-causing genes, overriding the animal’s natural resistance mechanisms.

The Cambridge team said they would continue to investigate the mechanisms by which the mole-rats stop cancer cells from developing into tumours, with the intention of revealing new ways of treating or preventing cancer in humans.

Dr Ewan St John Smith, one of the study’s senior authors, said: “All our work with naked mole-rats, from studying their hypoxia resistance to pain insensitivity and cancer resistance, is aiming to leverage the extreme biology of this species to understand more about how our bodies work normally.”

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