Sympathetic nervous system regulation of the tumour microenvironment

Activation of the peripheral nervous system can promote metastasis of primary tumours. This Opinion article discusses the molecular mechanisms through which physiological stress can have an effect on cancer, and how pharmacological antagonism of β-adrenergic signalling might represent a therapeutic opportunity to target cancer progression. 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.