Naked mole rats are living long cancer-free lives, and now we know why

moleBy: Chloe Nevitt
It’s not surprising to hear the word rat associated with scientific research. Of course, most people immediately imagine the red-eyed furry white lab rat that runs through mazes. However, recent cancer research has focused the microscope on its’ furless cousin, the naked mole rat.
These sausage-like creatures live in huge underground colonies, centered on a queen, similar to ants. Some of the moles are responsible for foraging for food for the colony, while others tend to the queen. While blind mole rats do possess eyes, they are located beneath the skin and fur, and instead they rely on sensitive hairs found on the ends of their snouts to find their way.
The naked mole rat also has an astonishingly long life span, upward of 30 years, and is apparently cancer-resistant. Not a single incidence in cancer in the African rodent has been found, ever. Compared to their lab rat cousins, whose life spans hover around four years and are extraordinarily cancer prone – a 47% cancer rate, these curious observations make the naked mole rat a novel model for new cancer-fighting methods.
Scientists went searching for the answer. A team at the University of Rochester attempted to trigger cancer in naked mole rats by infecting them with viruses known to commonly cause cancers in mice and rats. Dr. Gorbunova and Dr. Seluanov, a husband-and-wife team of biologists at Rochester, then tried growing the cells in culture mediums. Here, they began to uncover the naked mole rats’ secret.
The naked mole rats cells stopped growing at a third of the density that mouse cells do. They also noticed that the nutritional medium they were in, after a few days, turned into syrup. “We need to find out what this goo is,” said Dr. Gorbunova. Their postdoctoral researcher, Christopher Hine, discovered that the goo was composed of a large polymer called Hyaluronan.
The team at the University of Rochester found, simultaneously as scientists at the University of Haifa, was the Hyaluronan in naked mole rats was five times as large as human Hyaluronan. This sugar was called high-molecular-mass Hyaluronan (HMM-HA). HMM-HA is a form of Hyaluronan, a polysaccharide found in the extracellular matrix and soft connective tissue. Commonly found in humans, it is responsible for signaling and elasticity.
HMM-HA secretion by naked mole rat cells has been shown to prevent overcrowding and the formation of tumours. “Experiments showed that when HMM-HA was removed from naked mole rat cells, they became susceptible to tumours and lost their contact inhibition.” Explains Prof. Eviatar Nevo, from the Institute of Evolution at the University of Haifa.
Contact inhibition when observed in normal cells is the arrest of growth when two cells’ plasma membranes touch. Cancer cells, on the other hand, will continue to grow until overtaking the other cells, ultimately creating a tumour.
HMM-HA in naked mole rats also accumulates in abundant amounts, owing to decreased enzymatic degradation and increased synthesis by a protein called HAS2. On a genetic level, theHas2 naked mole rat gene differs in sequence by only two amino acids, this substitution perhaps the reason for its’ high output levels.
When the scientists shut down this gene in naked mole rats and then inserted a cancer-causing virus, the hyaluronan-free cells multiplied uncontrollably. The researchers moved these cells into mice and watched as tumours developed. The new cells were just as cancer susceptible as the mouse, or human cells.
Researchers owe the increased HMM-HA as necessary for subterranean life. “If you grab an animal, it feels like you’re removing their skin,” Dr. Seluanov said. Stretchy skin is necessary for moving around in underground tunnels. And HA provides this elasticity.
While the questions of how exactly HA fights cancer and how increased levels of HA will react in human and mice cells have yet to be answered, we are perhaps on our way for new types of cancer prevention.
 
 
 
 

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