TY - JOUR
T1 - Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth
AU - Armaiz-Pena, Guillermo N.
AU - Gonzalez-Villasana, Vianey
AU - Nagaraja, Archana S.
AU - Rodriguez-Aguayo, Cristian
AU - Sadaoui, Nouara C.
AU - Stone, Rebecca L.
AU - Matsuo, Koji
AU - Dalton, Heather J.
AU - Previs, Rebecca A.
AU - Jennings, Nicholas B.
AU - Dorniak, Piotr
AU - Hansen, Jean M.
AU - Arevalo, Jesusa M.G.
AU - Cole, Steve W.
AU - Lutgendorf, Susan K.
AU - Sood, Anil K.
AU - Lopez-Berestein, Gabriel
PY - 2015
Y1 - 2015
N2 - Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production.
AB - Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production.
KW - Catecholamines
KW - MCP1
KW - Macrophages
KW - Monocytes
KW - Ovarian cancer
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U2 - 10.18632/oncotarget.2887
DO - 10.18632/oncotarget.2887
M3 - Article
C2 - 25738355
AN - SCOPUS:84924250608
SN - 1949-2553
VL - 6
SP - 4266
EP - 4273
JO - Oncotarget
JF - Oncotarget
IS - 6
ER -