Israel's Weizmann Institute scientists discover a control mechanism for metastasis
- From: "The Pragmatist" <pragmatist@xxxxxxxxxxxx>
- Date: Thu, 16 Aug 2007 07:16:34 GMT
An amazing breakthrough by scientists at Israel's prestigious Weizmann
Institute...Some 90% of cancer deaths are not due to local tumors, but to
the process of metastasis. Particularly varieties of cancer have a
predilection to spread to specific target organs. This is a very hot area of
current research. From
http://cancerfocus.net/weizmann_institute_scientists_discover_a_control_mechanism_for_metastasis/576
Viva Israel!!!! An amazing nation with an incredibly talented population.
Weizmann Institute scientists discover a control mechanism for metastasis
Submitted by Dross on Wed, 2007-08-08 21:15. More on: metastisis
Weizmann Institute scientists discover a control mechanism for metastasis
similarity
Metastasisterm - when cancer cells dissociate from the original tumor and
migrate via the blood stream to colonize 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 a cell such as a cancer 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.' This signal takes the form of a substance called
a growth factor, which, in addition to controlling movement, can activate a
number of processes in the cell including division and differentiation. 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 protein fibers - comes apart and the protein
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 less.
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. This team, headed by
Prof. Yosef Yarden of the Weizmann Institute's Biological Regulation
Department and his research group, including Drs. Menachem Katz, Ido Amit
and Ami Citri; Tal Shay, a student in the group of Prof. Eytan Domany of the
Physics of Complex Systems Department; and Prof. Gideon Rechavi of the Chaim
Sheba Medial Center at Tel Hashomer.
To begin with, the 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 they received, including details on every
protein level that went up or down, one family of proteins 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 skeleton, 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 skeletal 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 influences 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 associated with elevated growth factor levels.
The scientists found a strong correlation between high growth factor
activity and levels of the 'plug' protein. High levels of this protein, in
turn, were associated with cancer metastasis to the lymph nodes - the first
station of migrating cancer cells as they spread to other parts of the body.
In another experiment, the scientists examined the effects of drugs that
block the growth factor receptors on the cell walls. In patients who
received these drugs, the harmful 'plug' proteins had disappeared from the
cancer cells. Prof. Yarden: 'The mechanism we identified is clinically
important. It can predict the development 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 thus prevent metastasis in breast or other cancers.
.
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