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Spreading Cancer Survives Via Signals From Nearby Blood Vessels Long Before New Vessels Are Grown

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Duke Health News 919-660-1306

DURHAM, N.C. -- In one of the clearest models of cancer metastasis,
scientists have shown that spreading cancer cells receive
growth-sustaining signals from nearby blood vessels telling them where
to go for permanent nourishment and oxygen.

These signals
actually protect the fledgling cancer cells long before new blood
vessels have grown around the cancer to supply it with a more permanent
source of nutrients and oxygen, said the researchers from the Duke
Comprehensive Cancer Center.

Their results will be published in
the Dec. 19, 2003, issue of the Federation of American Societies for
Experimental Biology Journal.

"We've demonstrated a give and take
relationship in which cancer cells release signals to nearby blood
vessels to stimulate new vessel growth, and in turn, blood vessels
release signals that sustain the migrating cancer cells as they try to
establish themselves in new tissue," said Duke cancer biologist Mark
Dewhirst, Ph.D.

Dewhirst said his findings present a model of the
earliest stages of cancer metastasis, and they bolster medicine's
latest strategy of blocking blood vessel growth as a means of
inhibiting cancer's spread.

Scientists have long known that
tumors secrete proteins which promote the growth of new blood vessels
to sustain the tumor's continued growth. What they didn't realize is
that endothelial cells that line the blood vessels are also releasing
signals back to the cancer cells that protect the cancer cells from
dying and direct them to grow toward the blood vessel.

In fact,
the cancer cells respond to the endothelial cells' messages by
elongating and stretching toward the blood vessel in a column
formation, their study showed. This change occurs within days after the
cancer cells are implanted in the tissue, and long before new blood
vessels have begun to form.

"Our data show that blood vessel
endothelial cells are involved in cancer survival and growth at a far
earlier stage than we had originally believed," said Dewhirst. "This
discovery energizes our efforts to block these signals from being
released and to inhibit new blood vessels from forming." Such a
strategy is called anti-angiogenesis.

The two-way dialogue begins
when cancer cells secrete proteins -- such as vascular endothelial
growth factor (VEGF) and angiopoietin 2 -- that alert blood vessels to
their presence. These proteins prime the blood vessels to initiate new
blood vessel growth.

In response, blood vessel endothelial cells
release numerous growth and survival factors that sustain the tumor's
survival and invasion of the tissue, the study indicated.

Dewhirst's
team demonstrated this two-way dialogue between cancer cells and blood
vessels by testing how certain signals affected cancer cells in the
test tube and in animals. They found that:

* a signal called bFGF
(also known as a cytokine) known to promote cancer cell survival in the
body had no effect on cancer cells in a test tube. This finding shows
that bFGF is not directly acting on cancer cells, but instead it is
signaling another player -- probably endothelial cells in blood vessels
-- to induce cancer cell growth.

* the cancer cell models in the
current study do not even have bFGF receptors -- docking sites for
proteins to bind to and activate a reaction inside the cell. Without a
bFGF receptor, the bFGF protein cannot directly communicate the cancer
cell.

* when scientists prevented cancer cells from utilizing
VEGF -- a protein that prompts blood vessel growth –- they inhibited
cancer cell survival and growth long before new blood vessels had begun
to grow.

* by blocking a vessel-growth protein receptor called
Tie2, the scientists inhibited cancer cell survival long before new
blood vessels had begun to grow. This suggests that Tie2 is also
involved in promoting cancer survival, not just blood vessel growth.

Dewhirst
said these findings will help them block the earliest stages of cancer
metastasis -– or spreading from the primary tumor site –- because they
demonstrate how the fledgling metastatic cancer cell adapt and survive
in their new environment.

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