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EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma.
[liposarcoma]
Soft
tissue
sarcomas
(
STS
)
are
heterogeneous
malignant
tumors
of
mesenchymal
origin
.
Due
to
low
incidence
and
high
number
of
different
histological
subtypes
,
their
pathogenesis
and
thus
potential
targets
for
their
therapy
remain
barely
investigated
.
Several
studies
revealed
significant
higher
EPHB
4
expression
in
malignancies
such
as
prostate
and
colorectal
cancer
showing
survival
advantages
for
these
tumor
cells
.
Therefore
we
studied
the
expression
of
EPHB
4
in
a
total
of
46
clinical
human
specimens
of
different
STS
and
human
fibroblasts
.
EPHB
4
mRNA
and
protein
expression
were
significantly
increased
in
synovial
sarcoma
.
After
targeting
EPHB
4
in
fibrosarcoma
,
synovial
sarcoma
,
liposarcoma
and
MFH
sarcoma
cell
lines
by
siRNA
or
by
inhibition
of
autophosphorylation
using
the
specific
EPHB
4
kinase
inhibitor
NVP-BHG
712
a
decreased
proliferation
rate
/
vitality
of
synovial-
and
fibrosarcoma
cells
was
observed
.
Silencing
of
EPHB
4
significantly
reduced
the
transmigration
of
synovial
sarcoma
cells
towards
fibroblasts
and
endothelial
cells
.
In
addition
,
we
assessed
the
anti-metastatic
effect
of
EPHB
4
inhibition
in
vivo
by
intraperitoneal
administration
of
the
EPHB
4
inhibitor
in
an
appropriate
sarcoma
lung
metastasis
xenograft
model
.
As
result
43
%
of
NVP-BHG
712
treated
mice
(
n
=
3
/
7
)
developed
pulmonary
metastases
whereas
all
control
mice
(
n
=
5
)
revealed
lung
metastases
.
The
residual
57
%
of
mice
(
n
=
4
/
7
)
showed
only
small
local
tumor
cell
spots
.
Size
measurements
of
the
Vimentin
positive
area
explained
significant
decrease
in
lung
metastasis
formation
(
p
<
0
.
05
)
after
EPHB
4
kinase
inhibition
.
In
summary
,
these
data
provide
first
evidence
of
the
importance
of
EPHB
4
in
the
tumorigenesis
of
synovial
sarcoma
and
present
EPHB
4
as
a
potential
target
in
the
therapy
of
this
malignancy
.
Diseases
Validation
Diseases presenting
"tumor cells"
symptom
alpha-thalassemia
carcinoma of the gallbladder
cholangiocarcinoma
cushing syndrome
dedifferentiated liposarcoma
dentin dysplasia
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
junctional epidermolysis bullosa
kindler syndrome
liposarcoma
lymphangioleiomyomatosis
pleomorphic liposarcoma
primary effusion lymphoma
severe combined immunodeficiency
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
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