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Nat Rev Cancer. 2015 Sep;15(9):563-72. doi: 10.1038/nrc3978.

Sympathetic nervous system regulation of the tumour microenvironment.

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Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles (UCLA) Molecular Biology Institute, 11-934 Factor Building, UCLA School of Medicine, Los Angeles California 90095-1678, USA; and the Jonsson Comprehensive Cancer Center, UCLA, 8-684 Factor Building, Box 951781, Los Angeles, California 90095-1781, USA.
Department of Gynecologic Oncology; and the Department of Cancer Biology, University of Texas M. D. Anderson Comprehensive Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Department of Psychology, E11 Seashore Hall, Department of Obstetrics and Gynecology, 200 Hawkins Drive; Department of Urology, 3 Roy Carver Pavilion, 200 Hawkins Drive; and the Holden Comprehensive Cancer Center, 200 Hawkins Drive, University of Iowa, Iowa City 52242-1407, USA.
Basic Biobehavioral and Psychological Sciences Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, United States National Cancer Institute, Building 9609 Room 3E133, 9609 Medical Center Drive, Rockville, Maryland 20850, USA.


The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programmes that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and haematopoietic differentiation programmes. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacological strategies to inhibit cancer progression in vivo.

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