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Sympathetic nervous system regulation of the tumour microenvironment

Abstract

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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Figure 1: Sympathetic nervous system regulation of the tumour microenvironment.
Figure 2: Molecular mechanisms for sympathetic nervous system regulation of tumour progression.

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Acknowledgements

This work was supported by grants from the United States National Institutes of Health (CA083639, CA098258, CA104825, CA109298, CA116778, CA140933, CA151668, CA177909, AG017265, AG033590) and Department of Defense (OC120547, OC093416), the Betty Ann Asche Murray Distinguished Professorship, the Cancer Prevention and Research Institute of Texas (CPRIT RP140106), and the Breast Cancer Research Foundation.

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Correspondence to Steven W. Cole.

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Cole, S., Nagaraja, A., Lutgendorf, S. et al. Sympathetic nervous system regulation of the tumour microenvironment. Nat Rev Cancer 15, 563–572 (2015). https://doi.org/10.1038/nrc3978

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