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 programs 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 hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo.

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

“…Mounting clinical and preclinical evidence has shown that psychosocial factors can trigger chronic adrenergic signaling within tumors and promote tumor growth and metastasis in many tumor types (1)(2)(3)(4)(5). Activation of the sympathetic nervous system leads to release of stress hormones such as epinephrine and norepinephrine (NE), which signal via adrenergic receptors on tumor cells, resulting in diminished efficacy of conventional chemotherapy and promotion of tumor metastasis, inflammation, and other prosurvival pathways (6)(7)(8)(9)(10)(11)(12).…”

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

“…Perhaps these processes are also associated with aspects of cancer pathogenesis. Specifically, breast cancer tumors initiate neurogenesis and release nerve growth factor (Cole, Nagaraja, Lutgendorf, Green, & Sood, 2015; Pundavela et al., 2015; Zhao et al., 2014), which may result in aberrant CNS activity via peripheral innervation. Tumor aggressiveness has been associated with tumor‐related neurogenesis (Zhao et al., 2014).…”

“…Stress is also associated with disrupted functional dynamics in patients with breast cancer, inflammatory response, and tumor progression (Churchill et al., 2015; Cole et al., 2015). Psychological distress, as measured by CAD, was significantly higher in the breast cancer group compared to controls, but was not a significant contributor to group differences in cognitive performance and was not correlated with Hurst long memory or structure–function component.…”

Thermoneutrality, Mice, and Cancer: A Heated Opinion

“…These changes were recapitulated by treatment of cell lines in vitro with a b-AR agonist, thus confirming a direct effect of adrenergic signaling on tumor cells themselves. The tumor-promoting effect of adrenergic signaling has been reviewed recently [49,50], but the ability of ST to cause this degree of stress is generally unrecognized. Moreover, tumors in mice housed at TT were significantly more sensitive to Apo2L/TRAIL, cisplatin, and nab-paclitaxel (Abraxane) than were tumors in mice at ST.…”