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CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease.
[severe combined immunodeficiency]
Secreted
protein
CCN
1
,
encoded
by
CYR
61
,
is
involved
in
wound
healing
,
angiogenesis
,
and
osteoblast
differentiation
.
We
identified
CCN
1
as
a
microenvironmental
factor
produced
by
mesenchymal
cells
and
overexpressed
in
bones
of
a
subset
of
patients
with
monoclonal
gammopathy
of
undetermined
significance
(
MGUS
)
,
asymptomatic
myeloma
(
AMM
)
,
and
multiple
myeloma
(
MM
)
.
Our
analysis
showed
that
overexpression
of
CYR
61
was
independently
associated
with
superior
overall
survival
of
MM
patients
enrolled
in
our
Total
Therapy
3
protocol
.
Moreover
,
elevated
CCN
1
was
associated
with
a
longer
time
for
MGUS
/
AMM
to
progress
to
overt
MM
.
During
remission
from
MM
,
high
levels
of
CCN
1
were
associated
with
superior
progression-free
and
overall
survival
and
stratified
patients
with
molecularly
defined
high
-risk
MM
.
Recombinant
CCN
1
directly
inhibited
in
vitro
growth
of
MM
cells
,
and
overexpression
of
CYR
61
in
MM
cells
reduced
tumor
growth
and
prevented
bone
destruction
in
vivo
in
severe
combined
immunodeficiency
-
hu
mice
.
Signaling
through
αvβ
3
was
required
for
CCN
1
prevention
of
bone
disease
.
CYR
61
expression
may
signify
early
perturbation
of
the
microenvironment
before
conversion
to
overt
MM
and
may
be
a
compensatory
mechanism
to
control
MM
progression
.
Therapeutics
that
upregulate
CYR
61
should
be
investigated
for
treating
MM
bone
disease
.
Diseases
Validation
Diseases presenting
"tumor growth"
symptom
adrenal incidentaloma
carcinoma of the gallbladder
cholangiocarcinoma
cowden syndrome
cystinuria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
liposarcoma
lymphangioleiomyomatosis
primary effusion lymphoma
severe combined immunodeficiency
von hippel-lindau disease
waldenström macroglobulinemia
wiskott-aldrich syndrome
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