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Complement Factor I Promotes Progression of Cutaneous Squamous Cell Carcinoma.
[dystrophic epidermolysis bullosa]
The
incidence
of
cutaneous
squamous
cell
carcinoma
(
cSCC
)
is
rising
worldwide
.
We
have
examined
the
role
of
complement
components
in
the
progression
of
cSCC
.
Analysis
of
cSCC
cell
lines
(
n
=
8
)
and
normal
human
epidermal
keratinocytes
(
n
=
11
)
with
whole
transcriptome
profiling
(
SOLiD
)
,
quantitative
real-time
reverse
transcriptase-
PCR
,
and
western
blotting
revealed
marked
overexpression
of
complement
factor
I
(
CFI
)
in
cSCC
cells
.
Immunohistochemical
analysis
for
CFI
in
vivo
showed
stronger
tumor
cell-
specific
labeling
intensity
in
invasive
sporadic
cSCCs
(
n
=
83
)
and
recessive
dystrophic
epidermolysis
bullosa
-associated
cSCCs
(
n
=
7
)
than
in
cSCC
in
situ
(
n
=
65
)
,
premalignant
epidermal
lesions
(
actinic
keratoses
,
n
=
64
)
,
benign
epidermal
papillomas
(
seborrheic
keratoses
,
n
=
39
)
,
and
normal
skin
(
n
=
9
)
.
The
expression
of
CFI
was
higher
in
the
aggressive
Ha-ras-transformed
cell
line
(
RT
3
)
than
in
less
tumorigenic
HaCaT
cell
lines
(
HaCaT
,
A
5
,
and
II
-
4
)
.
The
expression
of
CFI
by
cSCC
cells
was
upregulated
by
IFN-γ
and
IL
-
1
β
.
Knockdown
of
CFI
expression
inhibited
proliferation
and
migration
of
cSCC
cells
and
resulted
in
inhibition
of
basal
extracellular
signal-regulated
kinase
(
ERK
)
1
/
2
activation
.
Knockdown
of
CFI
expression
potently
inhibited
growth
of
human
cSCC
xenograft
tumors
in
vivo
.
These
results
provide
evidence
for
the
role
of
CFI
in
the
progression
of
cSCC
and
identify
it
as
a
potential
therapeutic
target
in
this
nonmelanoma
skin
cancer
.
Journal
of
Investigative
Dermatology
advance
online
publication
,
2
October
2014
;
doi
:
10
.
1038
/
jid
.
2014
.
376
.
Diseases
Validation
Diseases presenting
"invasive sporadic csccs"
symptom
dystrophic epidermolysis bullosa
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