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New research shows common
drug prevents cancer spread
SAN DIEGO -- Mar. 12, 2001 -- A common drug
used to prevent blood clots diminishes the spread of certain
cancers in mice by cloaking the tumor cells in protective coating
that shields them from the immune cells that would normally destroy
them say researchers in San Diego. The finding dramatically alters
current thinking about how the drug works.
In the study, the drug, heparin, was shown
to interfere with interactions between platelets, the type of
normal blood cells that cause clotting to stop bleeding, and
specific molecules on tumor cell surfaces. The work also suggests
that the early phase of these interactions is crucial for metastasis,
the process in which cancer cells break away from the tumor,
enter the bloodstream and travel to distant tissues and establish
new tumors. Metastasis eventually kills most patients with cancer.
Writing in the March 13 issue of the Proceedings
of the National Academy of Sciences, the research team led
by senior author Dr. Ajit Varki say their findings make a compelling
argument for initiating clinical trials of heparin in patients
with newly diagnosed cancer.
"The notion of using anticoagulants to
inhibit metastasis is not new," said the study authors in
a prepared statement. "However, our new findings suggest
that heparin therapy to prevent the spread of cancer in humans
should be revisited with a completely new paradigm in mind."
Animal studies in the 1960s and 1970s showed
that heparin delivered by injection or intravenously inhibits
metastasis. Follow-up human studies focused instead on the use
of oral anticoagulants, which are easier to manage than heparin.
Those attempts failed, however, and research in this area stalled.
Other mechanisms for the heparin effect have since been suggested,
but not proven.
The new research, led by Dr. Lubor Borsig,
a postdoctoral fellow working in Varki's laboratory, details
heparin's precise mechanism and explains why earlier clinical
trials using oral anticoagulants failed.
Experimental mice received a single dose of
heparin, which lasted for only a few hours, yet this early exposure
resulted in markedly reduced cancer cell survival and metastasis
when the mice were examined several weeks later.
When Borsig examined the mechanism for this
phenomenon, he found that as the cancer cells break away from
the original tumor and enter the bloodstream they attract platelets,
which bind to sugarcoated molecules called mucins on the cancer
cell surface, forming a cloak.
This platelet cloak appears to protect the
tumor cells from the body's natural defense systems, enabling
them to establish new tumors in other parts of the body. Heparin
interferes with formation of the platelet cloak, apparently leaving
tumor cells exposed to attack by white blood cells.
"Our findings show that the anti-metastatic
effect of heparin is not due to its ability to prevent blood
clotting, as was previously thought, but rather its blockage
of early tumor-platelet interactions in the bloodstream,"
said Borsig. "Oral anticoagulants work by a completely different
mechanism and do not block these interactions."
SOURCE: University of California San Diego
press release
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