Molecular Cancer Research,
Год журнала:
2010,
Номер
8(5), С. 629 - 642
Опубликована: Май 12, 2010
Cell
migration
and
invasion
are
critical
parameters
in
the
metastatic
dissemination
of
cancer
cells
formation
metastasis,
major
cause
death
patients.
Migratory
undergo
dramatic
molecular
cellular
changes
by
remodeling
their
cell-cell
cell-matrix
adhesion
actin
cytoskeleton,
processes
that
involve
activity
various
signaling
networks.
Although
past
years,
we
have
substantially
expanded
our
knowledge
on
underlying
cell
experimental
systems,
still
lack
a
clear
understanding
how
disseminate
Different
types
seem
to
exist,
including
single-cell
mesenchymal
or
amoeboid
collective
migration.
In
most
epithelial
cancers,
loss
molecule
E-cadherin
gain
markers
promigratory
signals
underlie
conversion
epithelial,
differentiated
mesenchymal,
migratory,
invasive
cells,
process
referred
as
epithelial-to-mesenchymal
transition.
solitary
migrating
mostly
undergone
transition
(mesenchymal
migration),
sometimes
even
lose
(amoeboid
sheets,
clusters,
streams
is
also
frequently
observed.
The
mechanisms
defining
different
modes
remain
parts
be
delineated.
FEBS Journal,
Год журнала:
2010,
Номер
278(1), С. 16 - 27
Опубликована: Окт. 21, 2010
Matrix
metalloproteinases
(MMPs)
consist
of
a
multigene
family
zinc-dependent
extracellular
matrix
(ECM)
remodeling
endopeptidases
implicated
in
pathological
processes,
such
as
carcinogenesis.
In
this
regard,
their
activity
plays
pivotal
role
tumor
growth
and
the
multistep
processes
invasion
metastasis,
including
proteolytic
degradation
ECM,
alteration
cell-cell
cell-ECM
interactions,
migration
angiogenesis.
The
underlying
premise
current
minireview
is
that
MMPs
are
able
to
proteolytically
process
substrates
milieu
and,
so
doing,
promote
progression.
However,
certain
members
MMP
exert
contradicting
roles
at
different
stages
during
cancer
progression,
depending
among
other
factors
on
stage,
site,
enzyme
localization
substrate
profile.
therefore
amenable
therapeutic
intervention
by
synthetic
natural
inhibitors,
providing
perspectives
for
future
studies.
Multiple
agents,
called
metalloproteinase
inhibitors
(MMPIs)
have
been
developed
target
MMPs,
attempting
control
enzymatic
activity.
Even
though
clinical
trials
with
these
compounds
do
not
show
expected
results
most
cases,
field
MMPIs
ongoing.
This
critically
evaluates
relation
highlights
challenges,
well
prospects,
design,
development
efficacy
MMPIs.
The Journal of Cell Biology,
Год журнала:
2013,
Номер
201(7), С. 1069 - 1084
Опубликована: Июнь 24, 2013
Cell
migration
through
3D
tissue
depends
on
a
physicochemical
balance
between
cell
deformability
and
physical
constraints.
Migration
rates
are
further
governed
by
the
capacity
to
degrade
ECM
proteolytic
enzymes,
particularly
matrix
metalloproteinases
(MMPs),
integrin-
actomyosin-mediated
mechanocoupling.
Yet,
how
these
parameters
cooperate
when
space
is
confined
remains
unclear.
Using
MMP-degradable
collagen
lattices
or
nondegradable
substrates
of
varying
porosity,
we
quantitatively
identify
limits
arrest.
MMP-independent
declined
as
linear
function
pore
size
with
deformation
nucleus,
arrest
reached
at
10%
nuclear
cross
section
(tumor
cells,
7
µm2;
T
4
neutrophils,
2
µm2).
Residual
under
restriction
strongly
depended
upon
MMP-dependent
cleavage
enlarging
diameters,
actomyosin-dependent
force
generation,
which
jointly
propelled
nucleus.
The
interstitial
thus
depend
scaffold
porosity
pericellular
collagenolysis
mechanocoupling
modulators.
Journal of Clinical Investigation,
Год журнала:
2012,
Номер
122(3), С. 899 - 910
Опубликована: Фев. 1, 2012
Appropriate
localization
and
migration
of
T
cells
is
a
prerequisite
for
antitumor
immune
surveillance.
Studies
using
fixed
tumor
samples
from
human
patients
have
shown
that
accumulate
more
efficiently
in
the
stroma
than
islets,
but
mechanisms
by
which
this
occurs
are
unknown.
By
combining
immunostaining
real-time
imaging
viable
slices
lung
tumors,
we
revealed
density
orientation
stromal
extracellular
matrix
likely
play
key
roles
controlling
cells.
Active
cell
motility,
dependent
on
chemokines
not
β1
or
β2
integrins,
was
observed
loose
fibronectin
collagen
regions,
whereas
migrated
poorly
dense
areas.
Aligned
fibers
perivascular
regions
around
epithelial
dictated
migratory
trajectory
restricted
them
entering
islets.
Consistently,
reduction
with
collagenase
increased
ability
to
contact
cancer
Thus,
influences
immunity
positioning
Understanding
network
generated
has
potential
aid
development
new
therapeutics.
Mutation Research/Reviews in Mutation Research,
Год журнала:
2011,
Номер
728(1-2), С. 23 - 34
Опубликована: Май 20, 2011
Metastasis
is
the
leading
cause
of
cancer
mortality.
The
metastatic
cascade
represents
a
multi-step
process
which
includes
local
tumor
cell
invasion,
entry
into
vasculature
followed
by
exit
carcinoma
cells
from
circulation
and
colonization
at
distal
sites.
At
earliest
stage
successful
dissemination,
primary
adapts
secondary
site
involving
tumor–stroma
crosstalk.
migration
plasticity
as
well
surrounding
environment
such
stromal
endothelial
are
mandatory.
Consequently,
mechanisms
movement
utmost
relevance
for
targeted
intervention
three
different
types
have
been
reported.
Tumor
can
migrate
either
collectively,
in
mesenchymal
or
an
amoeboid
type
intravasate
blood
lymph
vasculature.
Intravasation
interaction
with
vascular
endothelium
mechanistically
poorly
understood.
Changes
epithelial
enable
to
switch
between
these
motility.
may
change
depending
on
thereby
increasing
velocity
aggressiveness
invading
cells.
Interference
collective
invasion
targeting
integrin
expression
metalloproteinase
activity,
respectively,
resulted
phenotype
ultimate
strategy
There
little
mechanistic
details
reported
vivo
showing
that
behavior
be
reversed
efficiently
inhibited.
Future
concepts
metastasis
must
simultaneously
address
collective,
order
advance
anti-metastatic
strategies
coexist
cooperate.
Beyond
movements,
adhesion
stroma
heterotypic
circulating
emboli
paramount
therapy.
