Two researchers at the University of Rochester have discovered the chemical that makes naked
mole1 rats cancer-proof. The findings could eventually lead to new cancer treatments in people, said study authors Andrei Seluanov and Vera Gorbunova. Their research paper will be published this week in the journal Nature.
Naked mole rats are small, hairless,
subterranean2（地下的，秘密的） rodents3 that have never been known to get cancer, despite having a 30-year lifespan. The research group led by Seluanov and Gorbunova discovered that these rodents are protected from cancer because their tissues are very rich with high
molecular4 weight
hyaluronan（透明质酸） (HMW-HA).
The biologists' focus on HMW-HA began after they noticed that a
gooey（胶粘的） substance in the naked mole rat culture was
clogging5 the vacuum pumps and tubing. They also observed that, unlike the naked mole rat culture, other media containing cells from humans, mice, and
guinea pigs（豚鼠） were not
viscous6.
"We needed to understand what the goo was," said Seluanov.
Gorbunova and Seluanov identified the substance as HMW-HA, which caused them to test its possible role in naked mole rat's cancer resistance.
Seluanov and Gorbunova then showed that when HMW-HA was removed, the cells became
susceptible7 to tumors, confirming that the chemical did play a role in making naked mole rats cancer-proof. The Rochester team also identified the
gene8, named HAS2, responsible for making HMW-HA in the naked mole rat. Surprisingly, the naked mole rat gene was different from HAS2 in all other animals. In addition the naked mole rats were very slow at recycling HMW-HA, which contributed to the accumulation of the chemical in the animals' tissues.
The next step will be to test the effectiveness of HMW-HA in mice. If that test goes well, Seluanov and Gorbunova hope to try the chemical on human cells. "There's indirect evidence that HMW-HA would work in people," said Seluanov. "It's used in anti-wrinkle injections and to relieve pain from
arthritis9 in knee
joints10, without any
adverse11 effects. Our hope is that it can also induce an anti-cancer response."
"A lot of cancer research focuses on animals that are
prone12 to cancer," said Gorbunova. "We think it's possible to learn strategies for preventing tumors by studying animals that are cancer-proof."
Previous research by Seluanov and Gorbunova showed that the p16 gene in naked mole rats stopped the proliferation of cells when too many of them crowd together. In their latest work, the two biologists identified HMW-HA as the chemical that
activates13 the anti-cancer response of the p16 gene.
The research was supported by grants from the U.S. National Institutes of Health and the Ellison Medical Foundation.
Hyaluronan (HA), which makes tissues
supple14 and aids in the healing process, is found in high concentrations in the skin of naked mole rats. The biologists speculate that the rodents developed higher levels of HA in their skin to accommodate life in underground tunnels.
Future research from the Gorbunova and Seluanov labs will focus on determining whether the HMW-HA from naked mole rats may have clinical value for either treating or preventing cancer in humans.
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