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cientists have identified a
molecular mechanism through which an oral bacterium accelerates colorectal
cancer growth.
An oral bacterium with links to
tooth decay may speed up the growth of colorectal cancer.
Tests
have shown that around a third of people who develop colorectal cancer also
have the bacterium, which has the name Fusobacterium nucleatum. Their cancer also tends to be more aggressive,
but it was not clear why until the recent study.
A paper that
now features in the journal EMBO
Reports reveals how the microorganism promotes the growth of cancer
cells but not that of noncancerous cells.
The findings should help to clarify why some
colorectal cancers develop much faster than others, say the researchers who
hail from Columbia University in the City of New York.
The
team also identified a protein that could form the basis of a test for more
aggressive cancers and could lead to new treatments for colorectal and other
cancers.
Colorectal cancer and its development
According
to figures from the American Cancer Society, around 1 in 22
men and 1 in 24 women in the United States will receive a diagnosis of
colorectal cancer at some point in their lives.
At
the start of 2016, there were approximately 1.5 million people in the U.S. with
a history of colorectal cancer, some of whom were cancer free.
Colorectal
cancer develops from uncontrolled growth and survival of abnormal cells in the
colon or rectum, which are the final sections of the digestive, or
gastrointestinal, tract.
The
colon absorbs water and nutrients from what is left of food after it has
traveled through the stomach and small intestine. It then passes the remaining
waste to the rectum, which stores it ready for expulsion through the anus.
The most common precancerous stage of colorectal
cancer is a polyp, which is a growth that develops in the tissue that lines the
colon and rectum. Polyps grow very slowly, sometimes taking 20 years to
develop.
Most
polyps develop from cells that make up the glands that produce a lubricating
mucus in the colon and rectum. For this reason, they have the name adenomatous
polyps, or adenomas.
Adenomas
are very common, and around 33–50 percent of people will develop at least one.
However, while they can all become cancerous, less than 10 percent actually
become invasive.
Oral bacterium has role in colorectal cancer
Scientists
have known for some time that the abnormal cells that lead to cancerous
adenomas in colorectal cancer arise because of genetic mutations that build up
over time.
However,
more recently, they have increasingly observed that F. nucleatum, which often occurs in
tooth decay, also plays a significant role.
"Mutations,"
says senior study author Yiping W. Han, who is a professor of microbial
sciences in the College of Dental Medicine, "are just part of the
story."
"Other factors, including microbes, can also
play a role," she adds.
In
previous work, Prof. Han and her team found that F. nucleatum produces the molecule FadA adhesin, which sets
off a series of molecular events in colon cells that scientists have linked to
a number of cancers.
That
work also revealed that the protein only has this effect in cancerous colon
cells — it does not trigger these events in healthy colon cells.
Why the bacterium only acts on cancer cells
Prof.
Han says that the goal of the more recent study was to "find out why F. nucleatum only seemed to
interact with the cancerous cells."
The
researchers started the new work by studying noncancerous colon cells in
culture. They saw that these did not make the protein Annexin A1, which
promotes growth in cancer cells.
Further
tests in cell cultures and in mice revealed that blocking the protein
stopped F. nucleatumfrom
being able to attach to cancer cells, which stopped them growing so fast.
Another
set of tests also revealed that the microbe stimulates cancer cells to make
more Annexin A1, which in turn attracts more F. nucleatum.
"We
identified a positive feedback loop that worsens the cancer's
progression," Prof. Han explains. The cancer cells make Annexin A1 that
then attracts F. nucleatum,
the effect of which is to spur them to produce more of the protein.
"We propose a two-hit model,
where genetic mutations are the first hit. F. nucleatum serves as the second
hit, accelerating the cancer signaling pathway and speeding tumor growth."
Prof.
Yiping W. Han
The
research team's search of a national database yielded records on 466 people
with molecular details about their primary colon cancer. The
researchers found that those with higher levels of Annexin A1 fared worse, no
matter what their gender, age, or cancer grade and stage.
The
team intends to explore how to use Annexin A1 as a marker for identifying
aggressive colorectal cancer. There might also be opportunities for new
treatments for colorectal and other cancers that target the protein.
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