Researchers interested in learning how certain rodents manage to live long,
cancer-free lives have stumbled upon a potentially valuable clue: a substance
outside their cells seems to help stop malignancies from spreading.
Most research has focused on how cancer occurs inside cells. Studying the
area outside the cell, in what is called the "extracellular matrix", is new
territory, explained study co-author Vera Gorbunova, a professor of biology and
oncology at the University of Rochester, in Rochester, NY.
The substance the team studied is a molecule called hyaluronan. The rodents,
naked mole rats that are the size of mice, live about eight times longer than
rats and mice do. Unlike other mammals, they also have never been known to
develop cancer. As it turned out, naked mole rats have tissue rich in
Hyaluronan inhibits cancer growth
Hyaluronan is also a natural component of human tissues, and it is already
used to treat arthritis, cover skin in burn victims and as an ingredient in
anti-wrinkle creams, according to Gorbunova.
Hyaluronan works by binding to certain receptors that control cell behaviour.
Short forms of the molecule are associated with inflammation and cell growth,
while the longer form (the kind the naked mole rats possess) are not linked to
inflammation and prevent cell proliferation, Gorbunova explained.
In other words, for cancer cells to spread, they have to break out of the
tissue. Luckily for naked mole rats, their long molecules of hyaluronan prevent
that from happening.
Should the connection between the naked mole rat's form of hyaluronan and
cancer prevention be proven through further research, it's likely that humans
could get injections or pills that increase the amount of the molecule in their
bodies, said Gorbunova. The next step is to test the ability of hyaluronan to
stop the spread of cancer in mice, she added.
Thick and sticky
For the research the scientists began by looking at naked mole rat cells in a
growth medium in the laboratory. They noticed that their cells seemed to grow
differently than did others, allowing more space between other cells than
expected, said Gorbunova.
The investigators also realised that the growth medium was somehow becoming
unusually "gooey" after a couple of days. They knew that growth media with cells
from humans, guinea pigs and mice did not become thick and sticky.
But the scientists had no idea what could be transforming the consistency of
the growth medium. "When we saw the gooey media, I was pessimistic and thought
we'd never find out what it was," noted Gorbunova. But a graduate student
working on the research decided to simply "google" a description of what they
had found, and learned it was hyaluronan, she added.
Next, the researchers tested what would happen if they removed the
hyaluronan, and discovered that the cells then became susceptible to tumours,
confirming the role the molecule plays in "cancer-proofing" naked mole rats. The
scientists went on to identify the gene responsible for making hyaluronan, and
learned that it was not the same as in other mammals.
Hyaluronan, which makes tissue more elastic and facilitates the healing
process, is found in high concentrations in naked mole rats. The researchers
think the rodents may have developed high levels of the substance to make it
easier to squeeze through underground tunnels.
Gorbunova said scientists have been focusing on what was going on inside
cells, and now they may start studying the extracellular matrix. "Now there may
be a shift to understanding the extracellular environment as a key component in
cancer development," she said.
Vadim Gladyshev, director of the Center for Redox Medicine at Brigham and
Women's Hospital and Harvard Medical School, agreed. The discovery is "a little
bit unexpected because it's not the typical type of cancer research -- studying
the outside of cells -- rather than focusing on cell mechanisms and tumour
suppressors," he said.
Gladyshev has something in common with Gorbunova: He's been studying naked
mole rats, too. He published research two years ago that showed how he sequenced
the full genome of the rodents, looking for clues to their exceptionally long,
cancer-free lives. He thinks her findings should now be examined at the genomic
level to search for pathways associated with the function of hyaluronan. His
hope is that he can pursue that effort in cooperation with Gorbunova's team, he
Learn more about cancer from the US National
Library of Medicine.
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