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Endothelial-mesenchymal transition in normal human esophageal endothelial cells cocultured with esophageal adenocarcinoma cells: role of IL-1β and TGF-β2.
[esophageal adenocarcinoma]
Endothelial-mesenchymal
transition
(
EndoMT
)
has
been
recognized
as
a
key
determinant
of
tumor
microenvironment
in
cancer
progression
and
metastasis
.
Endothelial
cells
undergoing
EndoMT
lose
their
endothelial
markers
,
acquire
the
mesenchymal
phenotype
,
and
become
more
invasive
with
increased
migratory
abilities
.
Early
stages
of
esophageal
adenocarcinoma
(
EAC
)
are
characterized
by
strong
microvasculature
whose
impact
in
tumor
progression
remains
undefined
.
Our
aim
was
to
determine
the
role
of
EndoMT
in
EAC
by
investigating
the
impact
of
tumor
cells
on
normal
primary
human
esophageal
microvascular
endothelial
cells
(
HEMEC
)
.
HEMEC
were
either
cocultured
with
OE
33
adenocarcinoma
cells
or
treated
with
IL
-
1
β
and
transforming
growth
factor
-β
2
(
TGF-β
2
)
for
indicated
periods
and
analyzed
for
EndoMT-associated
changes
by
real-time
PCR
,
Western
blotting
,
immunofluorescence
staining
,
and
functional
assays
.
Additionally
,
human
EAC
tissues
were
investigated
for
detection
of
EndoMT-like
cells
.
Our
results
demonstrate
an
increased
expression
of
mesenchymal
markers
[
fibroblast-
specific
protein
1
(
FSP
1
)
,
collagen
1
α
2
,
vimentin
,
α-smooth
muscle
actin
(
α-
SMA
)
,
and
Snail
]
,
decreased
expression
of
endothelial
markers
[
CD
31
,
von
Willebrand
factor
VIII
(
vWF
)
,
and
VE-cadherin
]
,
and
elevated
migration
ability
in
HEMEC
following
coculture
with
OE
33
cells
.
The
EndoMT-related
changes
were
inhibited
by
IL
-
1
β
and
TGF-β
2
gene
silencing
in
OE
33
cells
.
Recombinant
IL
-
1
β
and
TGF-β
2
induced
EndoMT
in
HEMEC
.
Although
the
level
of
VEGF
expression
was
elevated
in
EndoMT
cells
,
the
angiogenic
property
of
these
cells
was
diminished
.
In
vivo
,
by
immunostaining
EndoMT-like
cells
were
detected
at
the
invasive
front
of
EAC
.
Our
findings
underscore
a
significant
role
for
EndoMT
in
EAC
and
provide
new
insights
into
the
mechanisms
and
significance
of
EndoMT
in
the
context
of
tumor
progression
.
Diseases
Validation
Diseases presenting
"tumor microenvironment in cancer"
symptom
esophageal adenocarcinoma
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