HEALTH & FITNESS
ORTHODONTICS
Controlling Cancer Cells
ADULTS & CHILDREN
Weizmann aims to slow metastasis.
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Steven M. Lash, DDS, MS
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etastasis — when can-
cer cells dissociate from
the original tumor and
migrate via the blood stream to colo-
nize distant organs — is the main
cause of cancer death.
A team of scientists at the
Weizmann Institute of Science has
now revealed new details about the
mechanisms controlling metastasis
of breast cancer cells. Their findings,
published recently online in Nature
Cell Biology, add significantly to the
understanding of metastasis and may
aid, in the future, in the development
of anti-cancer drugs.
For any cell to migrate, it first must
detach itself from neighboring cells
and the intercellular material to which
it is anchored. Before it can do this, it
receives an order from outside the cell
saying: "Prepare to move:'
The Growth Factor
This signal takes the form of a sub-
stance called a growth factor which
can activate a number of processes
in the cell including division and dif-
ferentiation.
The growth factor attaches to a
receptor on the cell wall, initiating a
sequence of changes in the cellular
structure. The cell's internal skeleton
— an assembly of densely-packed pro-
tein fibers — comes apart and the pro-
tein fibers then form thin threads on
the outside of the cell membrane that
push the cell away from its neighbors.
In addition, a number of protein
levels change: some get produced in
higher quantities and some in lower.
To understand which proteins are
modulated by the growth factor and
the nature of the genetic mechanisms
involved in cancer cell migration,
a team of researchers pooled their
knowledge and resources.
The Weizmann team mapped all of
the genetic changes that take place in
the cell after the growth factor signal
is received. As they sifted through the
enormous amount of data, includ-
ing details on every protein level that
went up or down, one family of pro-
teins stood out. Tensins, as they're are
called, are proteins that stabilize the
cell structure.
But to the scientists' surprise, the
amounts of one family member rose
dramatically while, at the same time,
the levels of another dropped.
Despite the familial similarity, the
team found a significant difference
between them. The protein that drops
off has two arms: One arm attaches
to the protein fibers forming the skel-
eton, and the other anchors itself to
the cell membrane. This action is what
stabilizes the cell's structure.
The protein that increases, on the
other hand, is made up of one short
arm that only attaches to the anchor
point on the cell membrane. Rather
than structural support, this protein
acts as a kind of plug, blocking the
anchor point and allowing the skel-
etal protein fibers to unravel into the
threads that push the cells apart.
The cell is then free to move, and,
if it's a cancer cell, to metastasize to a
new site in the body.
In experiments with genetically
engineered cells, the scientists showed
that the growth factor directly influ-
ences levels of both proteins and that
these, in turn, control the cells' ability
to migrate. Blocking production of the
short tensin protein kept cells in their
place, while overproduction of this
protein plug increased their migration.
Next, the scientists carried out tests
on tumor samples taken from around
300 patients with inflammatory breast
cancer, a rare but swift and deadly
form of the disease, which is associ-
ated with elevated growth factor levels.
The scientists found a strong correla-
tion between high growth factor activ-
ity and levels of the "plug" protein.
High levels of this protein, in turn,
were associated with cancer metasta-
sis to the lymph nodes — the first sta-
tion of migrating cancer cells as they
spread to other parts of the body.
The Weizmann team believes the
mechanism identified is clinically
important. It can predict the develop-
ment of metastasis and possibly how
the cancer will respond to treatment.
This discovery may, in the future,
aid in the development of drugs to
prevent or reduce the production of the
unwanted protein, and prevent metas-
tasis in breast or other cancers.