By Emily Dennis, @emilyjanedennis
Photo by Megan Murphy/Smithsonian’s National Zoo, creative commons.
Photo by Megan Murphy/Smithsonian’s National Zoo, creative commons.

Naked mole rats are neither moles, nor rats. They are mammals, but they live in bee-like colonies. They have eyes, but can barely see. They live for a long time (up to 30 years!) but rarely get cancer. Naked mole rats (above) are clearly not your average rodent. Now, thanks to a recent paper, we know that their cells aren’t really normal cells, either… and we have some tantalizing hints towards explaining why naked mole rats don’t get cancer.

Before researchers could study naked mole rat cells, they had to figure out how to grow them in the lab, outside of the animal. Many labs grow lots of different types of cells: bacteria from our stomachs, yeast from our beers, neurons from our brains, cancer cells from our tumors, and skin cells from our bodies… but until recently, no one could get naked mole rat cells to grow well.

When you try and grow naked mole rat cells in a dish filled with liquid food, like in the photo below, very few of the cells grow, and the ones that do make the food really sticky and viscous, like honey. Normally, with mouse or human cells, the dish fills with cells and the food remains fluid, like water.

Gooey naked mole rat cells in a dish. Photo by Brandon Vick/University of Rochester
Gooey naked mole rat cells in a dish. Photo by Brandon Vick/University of Rochester

Researchers at the University of Rochester were frustrated and interested by this gooey stuff, and set out to figure out what the cells were making that made the liquid food so sticky. Eventually, they found a molecule called hyaluronan which they thought might be making everything gooey. When they broke up hyaluronan, removed the gene for hyaluronan, or increased the amount of proteins that break down hyaluronan, the liquid food lost its stickiness.

Hyaluronan is usually found in the extracellular matrix, which is a set of gummy molecules that our cells excrete to help shape our tissues, and help with cell-to-cell communication. Hyaluronan is one of these gummy molecules. In humans, you can find hyaluronan in our joints, keeping them healthy, or in our skin, influencing how wrinkled we get as we age.

Because hyaluronan can act as a warning to tell other cells not to get too close, the presence of tons of hyaluronan is part of the reason why naked mole rat cells grow really far apart. This means if you have a small dish, only a few naked mole rat cells will grow in it, compared to tons of human cells or guinea pig cells. If you add a chemical that breaks up hyaluronan, the naked mole rat cells grow close together, just like the human and guinea pig cells.

hyaluronanSo, we already knew that hyaluronan is sticky, secreted by cells, and involved in keeping cells from growing too close together. It is hard to believe that no one checked to see if hyaluronan was the thing making naked mole rat cells gooey and hard to grow… but naked mole rats aren’t the only organisms that make hyaluronan. As I mentioned before, it’s in our joints and in our skin. This is probably the reason that no one considered this molecule: if hyaluronan can be found in humans and mice and guinea pigs and naked mole rats, why do only the naked mole rat cells get sticky?

In humans, different versions of hyaluronan have different functions: big hyaluronan molecules help stop more cells from growing and will help decrease inflammation. Small hyaluronan molecules, however, have the opposite effect — they encourage cells to grow. This paper shows us that naked mole rats have really, really big and potent versions of hyaluronan. Naked mole rat hyaluronan is at least four times bigger than the biggest hyaluronan found in humans.

This is the key: over evolutionary history, either human and guinea pig and mouse hyaluronan all got smaller, or something different happened to naked mole rats, selecting for bigger and bigger hyaluronan molecules over the generations.

A cell with tons of hyaluronan, which look like tentacles (Photo Credit: Kirsi Rilla)
A cell with tons of hyaluronan, which look like tentacles (Photo Credit: Kirsi Rilla)

The paper also discussed what this finding may mean for naked mole rats, and possibly for humans. Naked mole rats live really long, and almost never get cancer. Mice, on the other hand, live just a few years and almost all get cancer. The final experiments in this paper tested whether the removal of hyaluronan from naked mole rat cells would make them more like mouse cells when it comes to cancer.

In mice, we can make normal mouse cells into cancer-like cells by giving them a specific, cancer-causing virus. Injecting these cancer-like cells into a mouse gives them a tumor. If we give the same virus to naked mole rat cells, they don’t become cancerous. Injecting them into a mouse doesn’t lead to tumors. However, when researchers made naked mole rat cells that don’t make as much hyaluronan and then exposed them to the virus, they became cancer-like cells. When these cells were injected into mice, they caused tumors! This shows that hyaluronan can protect mice from getting this specific type of cancer.

For the long-term, researchers are now interested in seeing if giving mice and humans this naked mole rat form of hyaluronan can stop cancers from getting bigger or prevent cancers altogether. But of course, there’s a lot of research to be done before any conclusions can be made.

I have a soft spot for stories like this: as someone who studies mosquitoes, I love hearing stories about how studying really weird, specialized animals can give us unpredictable insights into how life works. This is an excellent example. Basic science FTW!

Check out the extra sources below on what this research was, what it means, and why you should care about it:

 

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