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Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles.
[liposarcoma]
Several
studies
have
shown
that
cancer
niche
can
perform
an
active
role
in
the
regulation
of
tumor
cell
maintenance
and
progression
through
extracellular
vesicles-based
intercellular
communication
.
However
,
it
has
not
been
reported
whether
this
vesicle-mediated
communication
affects
the
malignant
transformation
of
normal
stem
cells
/
progenitors
.
We
have
previously
reported
that
the
conditioned
medium
derived
from
the
mouse
Lewis
Lung
Carcinoma
(
LLC
)
cell
line
can
convert
mouse
induced
pluripotent
stem
cells
(
miPSCs
)
into
cancer
stem
cells
(
CSCs
)
,
indicating
that
normal
stem
cells
when
placed
in
an
aberrant
microenvironment
can
give
rise
to
functionally
active
CSCs
.
Here
,
we
focused
on
the
contribution
of
tumor
-derived
extracellular
vesicles
(
tEVs
)
that
are
secreted
from
LLC
cells
to
induce
the
transformation
of
miPSCs
into
CSCs
.
We
isolated
tEVs
from
the
conditioned
medium
of
LLC
cells
,
and
then
the
differentiating
miPSCs
were
exposed
to
tEVs
for
4
weeks
.
The
resultant
tEV
treated
cells
(
miPS-LLCev
)
expressed
Nanog
and
Oct
3
/
4
proteins
comparable
to
miPSCs
.
The
frequency
of
sphere
formation
of
the
miPS-LLCev
cells
in
suspension
culture
indicated
that
the
self-renewal
capacity
of
the
miPS-LLCev
cells
was
significant
.
When
the
miPS-LLCev
cells
were
subcutaneously
transplanted
into
Balb
/
c
nude
mice
,
malignant
liposarcomas
with
extensive
angiogenesis
developed
.
miPS-LLCevPT
and
miPS-LLCevDT
,
the
cells
established
from
primary
site
and
disseminated
liposarcomas
,
respectively
,
showed
their
capacities
to
self-renew
and
differentiate
into
adipocytes
and
endothelial
cells
.
Moreover
,
we
confirmed
the
secondary
liposarcoma
development
when
these
cells
were
transplanted
.
Taken
together
,
these
results
indicate
that
miPS-LLCev
cells
possess
CSC
properties
.
Thus
,
our
current
study
provides
the
first
evidence
that
tEVs
have
the
potential
to
induce
CSC
properties
in
normal
tissue
stem
cells
/
progenitors
.
Diseases
Validation
Diseases presenting
"first evidence"
symptom
congenital adrenal hyperplasia
dentin dysplasia
esophageal adenocarcinoma
fabry disease
homocystinuria without methylmalonic aciduria
krabbe disease
liposarcoma
phenylketonuria
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