Title:
Secreted phosphoprotein-1 directly provokes vascular leakage to foster
malignant pleural effusion
Languages of Item:
English
Abstract:
Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and
regulates tumor-associated angiogenesis and inflammation, both central
to the pathogenesis of malignant pleural effusion (MPE). Here, we
examined the impact of tumor- and host-derived SPP1 in MPE formation and
explored the mechanisms by which the cytokine exerts its effects. We
used a syngeneic murine model of lung adenocarcinoma-induced MPE. To
dissect the effects of tumor- versus host-derived SPP1, we
intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with
either wild-type or SPP1-deficient syngeneic lung cancer cells. We
demonstrated that both tumor- and host-derived SPP1 promoted pleural
fluid accumulation and tumor dissemination in a synergistic manner
(P<0.001). SPP1 of host origin elicited macrophage recruitment into the
cancer-affected pleural cavity and boosted tumor angiogenesis, whereas
tumor-derived SPP1 curtailed cancer cell apoptosis in vivo. Moreover,
the cytokine directly promoted vascular hyper-permeability independently
of vascular endothelial growth factor. In addition, SPP1 of tumor and
host origin differentially affected the expression of proinflammatory
and angiogenic mediators in the tumor microenvironment. These results
suggest that SPP1 of tumor and host origin impact distinct aspects of
MPE pathobiology to synergistically promote pleural fluid formation and
pleural tumor progression. SPP1 may present an attractive target of
therapeutic interventions for patients with MPE. Oncogene (2013) 32,
528-535; doi:10.1038/onc.2012.57; published online 27 February 2012
Authors:
Psallidas, I.
Stathopoulos, G. T.
Maniatis, N. A.
Magkouta,
S.
Moschos, C.
Karabela, S. P.
Kollintza, A.
Simoes, D.
C. M.
Kardara, M.
Vassiliou, S.
Papiris, S. A.
Roussos,
C.
Kalomenidis, I.
Publisher:
Nature Publishing Group
Keywords:
osteopontin; pleural effusion; cancer; inflammation; angiogenesis
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