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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 progression"
symptom
carcinoma of the gallbladder
cholangiocarcinoma
dedifferentiated liposarcoma
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
liposarcoma
pleomorphic liposarcoma
severe combined immunodeficiency
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
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