|
University
of
California,
San
Diego
New
Research
Shows
Common
Drug
-
Heparin
-
Prevents
Spread
of
Cancer
in
Mice
March
14,
2001
-
UCSD
Cancer
Center
researchers
have
obtained
evidence
that
the
common
anticoagulant
drug
heparin
diminishes
metastasis
of
certain
cancers
in
mice
by
interfering
with
interactions
between
platelets
(a
type
of
normal
blood
cell)
and
specific
molecules
on
tumor
cell
surfaces.
This
work
also
indicates
that
the
early
phase
of
these
interactions
is
crucial
for
metastasis
a
process
in
which
tumor
cells
from
the
primary
site
enter
the
bloodstream,
travel
to
distant
tissues
and
establish
new
tumors.
It
is
metastasis
that
eventually
kills
most
patients
with
cancer.
The
researchers,
who
report
their
work
in
the
March
13
issue
of
the
Proceedings
of
the
National
Academy
of
Sciences,
say
these
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
studys
senior
author
Ajit
Varki,
M.D.
"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
60s
and
70s
showed
that
heparin
which
is
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
Lubor
Borsig,
Ph.D.,
a
postdoctoral
fellow
working
in
Varkis
laboratory,
details
heparins
precise
mechanism
and
explains
why
earlier
clinical
trials
using
oral
anticoagulants
failed.
"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."
When
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
bodys
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.
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.
"This
demonstrates
that
the
early
phase
of
platelet-tumor
interaction,
crucial
for
metastasis,
can
be
inhibited
by
heparin,"
said
Borsig. |