TY - JOUR
TI - Expression of Interleukin-8 Receptor CXCR2 and Suppressor of Cytokine
Signaling-3 in Astrocytic Tumors
AU - Korkolopoulou, Penelope
AU - Levidou, Georgia
AU - El-Habr, Elias A. and
AU - Adamopoulos, Christos
AU - Samaras, Vassilis
AU - Zisakis, Athanasios and
AU - Kavantzas, Nikolaos
AU - Boviatsis, Efstathios
AU - Fragkou, Paraskevi and
AU - Papavassiliou, Athanasios G.
AU - Patsouris, Efstratios
AU - Piperi,
AU - Christina
JO - Current Molecular Medicine
PY - 2012
VL - 18
TODO - 3
SP - 379-388
PB - FEINSTEIN INST MED RES
SN - 1566-5240
TODO - 10.2119/molmed.2011.00449
TODO - null
TODO - The aim was to expand recently published information regarding the
significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and
activator of transcription) pathway in astrocytomas, focusing on the
IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the
STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of
91 paraffin-embedded human astrocytoma tissues (grades II-IV) were
investigated for the association of SOCS-3 and CXCR2 expression with
clinicopathologic and morphometric microvascular characteristics,
vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression
and patient survival. Peripheral IL-8 secretion levels were assessed by
enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2
protein levels were also quantified by Western immunoblotting in six
cases, and the protein levels of SOCS-3 and CXCR2 were correlated with
the immunohistochemical expression of the respective proteins. All
CXCR2-positive cases by Western immunoblotting displayed increased
peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell
cultures with exogenous IL-8 enhanced proliferation, and this effect was
inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3
and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78%
of cases, respectively, with their levels increasing with histological
grade and extent of necrosis. VEGF expression and microvessel density,
CXCR2 and IL-8 levels were interrelated, SOCS-3 and p-STAT-3 were
co-expressed in 85.7% of cases, although they were not interrelated. In
univariate survival analysis, increased SOCS-3 expression and the
presence of CXCR2 adversely affected survival, whereas in multivariate
analysis, only CXCR2 remained significant. The prognostic significance
of CXCR2 was validated in an independent set of 63 patients. Our data
implicate IL-8/CXCR2 signaling pathway in the progression and regulation
of angiogenesis in astrocytomas and provide a rationale for CXCR2
therapeutic exploitation in these tumors. Online address:
http://www.molmed.org doi: 10.2119/molmed.2011.00449
ER -