Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth.
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.
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Guillermo N
GN
Armaiz-Pena
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Vianey
V
Gonzalez-Villasana
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Archana S
AS
Nagaraja
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cristian
C
Rodriguez-Aguayo
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Nouara C
NC
Sadaoui
Department of Obstetrics and Gynecology, The John Hopkins University, Baltimore, MD 21287, USA.
Rebecca L
RL
Stone
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90089, USA.
Koji
K
Matsuo
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Heather J
HJ
Dalton
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Rebecca A
RA
Previs
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Nicholas B
NB
Jennings
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Piotr
P
Dorniak
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Jean M
JM
Hansen
Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, CA 90095, USA.
Jesusa M G
JM
Arevalo
Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, CA 90095, USA.
Steve W
SW
Cole
Department of Psychology, Obstetrics and Urology, and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, USA.
Susan K
SK
Lutgendorf
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Anil K
AK
Sood
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Gabriel
G
Lopez-Berestein
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009638:Norepinephrine / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D009638:Norepinephrine; D004837:Epinephrine