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Secret to possible cancer resistance discovered by upstate researchers

Brian Vick/University of Rochester

Researchers in upstate New York have identified the chemical that leads to cancer resistance in laboratory animals: naked mole rats.

The discovery could eventually lead to new cancer treatments, and even the ability for cancer resistance in humans according to the authors.

Biologists Andrei Seluanov and Vera Gorbunova from the University of Rochester identified the genes that make the rodents cancer-proof in 2009, but they were unsure what triggered those genes, until recently.

Resilient rodents hold health secrets

Naked mole rats are underground dwellers, native to East Africa, and live in a social hierarchy similar to a beehive. They have a queen, her group of favorite breeding males, soldiers who defend the tunnels and workers to build them.

Despite their less-than-appealing appearance, these peculiar mammals have proved to be of great interest to researchers as they possess many qualities relevant to human health. Naked mole rats have an extraordinary life span that is roughly ten times longer than that of a regular rodent like a mouse: roughly 30 years.

Additionally, they possess a gene that stops cancer cells from multiplying, preventing tumors from forming in their system. It was this gene, known as the P16 gene, which Seluanov and Gorbunova discovered four years ago.

Their new research paper, published in the journal Nature Wednesday, reveals the chemical responsible for triggering this cancer preventative gene. The chemical is known as high molecular weight hyaluronan(HMW-HA).

The findings demonstrate that high levels of HMW-HA in the tissues of naked mole rats makes them cancer-proof. The researchers say the chemical most probably evolved in such high levels in the rats because it makes the skin supple and aids in the healing process, properties conducive to their subterannean way of life.

Biologist Vera Gorbunova says HMW-HA functions by 'instructing' surrounding cells how to behave.

“It’s kind of like a phone call, so it instructs the cell what to do. And then the signal goes all the way inside the cell and then it can trigger various events,” she says.

Gorbunova says one event triggered by HMW-HA is a signal for cells to stop multiplying. This denys the opportunity for cancers to form or spread.

“We know now that when naked mole rat cells are surrounded by hyaluronan, that’s what tells them to stop dividing. We don’t yet know every single step of this cascade, but at least we know what the initial signal is,” Gorbunova says.

The team showed that when HMW-HA is removed, naked mole rat cells become susceptible to tumors. This confirmed their theory that the chemical does in fact play a role in making the rodents cancer-proof.

Hyaluronan in humans

During their research, Gorbunova and Seluanov also identified the gene responsible for producing the hyaluronan chemical which is called HAS2.

The remarkable thing about this gene and the chemical it produces, is that both are present in humans and other animals but in a different form. 

“[Hyaluronan is] a polymer molecule and naked mole rat’s polymer is longer," explains Gorbunova.

"Human bodies can accept this chemical, it’s sort of a natural part of us and it’s already used in the clinic for other applications like arthritis injections in the knees, in dermatology to cover the skin of burn victims. So potentially it can be applied to humans as an anti-cancer treatment.”

Gorbunova says the next step is to trial the impact of the 'naked mole rat gene' in mice.

“We are making a mouse that will express the naked mole rat gene for making hyaluronan and we will see if it lowers the cancer risk in these mice and maybe benefits them in some other ways,” she says.

“The mouse also has hyaluronan, it’s just shorter. What we want to see is, once we increase the size will it respond the same way as naked mole rat?”

If the mouse trials are successful, Gorbunova says they will look for ways to manipulate the HAS2 gene and the length of the hyaluronan polymer in humans, possibly through oral pills or injections.

Traditional research models won't help find resistance

Traditionally, cancer research focuses on animals prone to the disease, like mice. But Gorbunova highlights the need for more research to be centered around animals which already exhibit a natural resistance to cancer.

She stresses that it’s important to stray from the traditional research models when moving forward in cancer studies.

“Mice are only good to find ways to treat cancer once it’s already there because mice are much more prone to cancer than humans,” Gorbunova says.

“If you want to find how not to get cancer, a mouse is just not the place to look because they may not have the mechanisms to keep them tumor free. And that’s what inspired us to look at a species that naturally don’t get cancer because we thought, well here we may find mechanisms that maybe humans are lacking and maybe we could try to import those mechanisms in people.”

Gorbunova says future research from the team will focus on determining whether HMW-HA from naked mole rats may have clinical value for either treating or preventing cancer in humans.

She says the extraordinary longevity of the rodents lives also present an exciting area for research.

"To live long, it’s necessary not to get cancer but it’s not sufficient. And there may be many other mechanisms in addition to hyaluronan that make naked mole rats live ten times longer than other similar rodents.”

Gorbunova says research into the mechanisms present in naked mole rats could have great implications for breakthroughs in the health care arena.

WXXI/Finger Lakes Reporter for the Innovation Trail
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