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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
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated
