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Crosstalk between the mesothelium and lymphomatous cells: insight into the mechanisms involved in the progression of body cavity lymphomas.
[primary effusion lymphoma]
The
peculiar
localization
of
body
cavity
lymphomas
implies
a
specific
contribution
of
the
intracavitary
microenvironment
to
the
pathogenesis
of
these
tumors
.
In
this
study
,
primary
effusion
lymphoma
(
PEL
)
was
used
as
a
model
of
body
cavity
lymphoma
to
investigate
the
role
of
mesothelial
cells
,
which
line
the
serous
cavities
,
in
lymphoma
progression
.
The
crosstalk
between
mesothelial
and
lymphomatous
cells
was
studied
in
cocultures
of
primary
human
mesothelial
cells
(
HMC
)
with
PEL
cells
and
a
xenograft
mouse
model
of
peritoneal
PEL
.
PEL
cells
were
found
to
induce
type
2
epithelial-mesenchymal
transition
(
EMT
)
in
HMC
,
which
converted
into
a
myofibroblastic
phenotype
characterized
by
loss
of
epithelial
markers
(
pan
cytokeratin
and
E
-
cadherin
)
,
expression
of
EMT-associated
transcriptional
repressors
(
Snail
1
,
Slug
,
Zeb
1
,
Sip
1
)
,
and
acquisition
of
α-smooth
muscle
actin
(
α-
SMA
)
,
a
mesenchymal
protein
.
A
progressive
thickening
of
serosal
membranes
was
observed
in
vivo
,
accompanied
by
loss
of
cytokeratin
staining
and
appearance
of
α-
SMA
-expressing
cells
,
confirming
that
fibrosis
occurred
during
intracavitary
PEL
development
.
On
the
other
hand
,
HMC
were
found
to
modulate
PEL
cell
turnover
in
vitro
,
increasing
their
resistance
to
apoptosis
and
proliferation
.
This
supportive
activity
on
PEL
cells
was
retained
after
transdifferentiation
,
and
was
impaired
by
interferon-α
2
b
treatment
.
On
the
whole
,
our
results
indicate
that
PEL
cells
induce
type
2
EMT
in
HMC
,
which
support
PEL
cell
growth
and
survival
,
providing
a
milieu
favorable
to
lymphoma
progression
.
Our
findings
provide
new
clues
into
the
mechanisms
involved
in
lymphoma
progression
and
may
indicate
new
targets
for
effective
treatment
of
malignant
effusions
growing
in
body
cavities
.
Diseases
Validation
Diseases presenting
"loss of cytokeratin"
symptom
primary effusion lymphoma
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