Does sympathetic nervous system modulate tumor progression? A narrative review of the literature

Abstract

Objective: The role of the sympathetic nervous system (SNS) in tumor development, progression and metastasis is studied for more than half a century and is attracting more attention during the last years. In this narrative review, we aim to a chronological and methodological presentation of the most interesting and pioneering studies on the subject. Methods: The complexity of the autonomic nervous system's interaction with the immune system, its direct and indirect effects on tumors and their surrounding tissues, plus the diversity and heterogeneity in the design and methodology of the studies, provide hard-to-interpret data and, at times, controversial findings. Studies are categorized into four main groups regarding the distribution of sympathetic nerve fibers inside the tumor, the effect of sympathectomy on cancer progression, the role of neurotransmitters on tumor growth and the impact of sympathetic adrenergic signaling on the anti-tumor immune response. Results: Studies from all four categories converge to a common point. There is strong evidence that SNS function plays a role in the development and progression of tumors and subsequently the modification of SNS function, locally or diffusely, can affect the course of tumor growth. Conclusion: The impact of SNS function on cancer behavior may be exerted in two ways, directly via the sympathetic nerve fibers or through widely distributed neurotransmitters. Modification of them, combined or not with treatments altering the immune function, could be the target for future therapeutic implications.

Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization

“…Another possibility is that the contradictory findings arise from use of different experimental models and rat strains: naive Sprague Dawley (albino) in our prior study and laser-treated Brown Norway (pigmented) in the present studies (The laser-induced CNV model requires pigmented animals, since pigment is needed for absorbing the laser energy to create a burn). Yet another possibility is that sympathetic activity plays different roles in the intact versus leaky blood vessels, which is supported by a pro-angiogenic sympathetic role in tumor neovascularization ( Mulcrone et al, 2017 ; Hanns et al, 2019 ; Kamiya et al, 2019 ; Stavropoulos et al, 2020 ). In a comprehensive review of the role of the β-adrenergic system on ocular neovascularization, Casini et al (2014) concluded that “in different experimental models, a decrease of the β-adrenergic function may result either in reduction or in exacerbation of the vascular changes, thus suggesting possible dual effects of β-AR modulation depending on the experimental setting.” Because the laser-induced CNV model is the gold standard for testing new treatments for wet AMD ( Pennesi et al, 2012 ), future studies should focus on this model.…”

Expression of M3 muscarinic acetylcholine receptors in gastric cancer

“…The increase in the density of parasympathetic nerve endings, M3 mAChR and vesicular ACh transporter (VAChT) was also correlated with progression, unfavorable prognosis and vascular metastasis in liver cancer [ 35 ]. In prostate cancer, M3 mAChR overexpression causes castration-resistant prostate cancer (CRPC) by YAP pathway, high levels of IL-8 are associated with angiogenesis and metastases [ 36 ], while depression is a high-risk factor for unfavorable outcome [ 37 ].…”

Stress in Metastatic Breast Cancer: To the Bone and Beyond

“…Indeed, stress is a complex process where both psychosocial and environmental factors trigger a cascade of information-processing pathways in the central and peripheral nervous system [50]. Both the hypothalamic-pituitary-adrenal (HPA) axis and the SNS systems have been implicated in cancer, supported by an increasing body of studies linking the "fight-or-flight" stress response of SNS mediators with cancer progression [21,22,[51][52][53]. For this reason, the investigation on the role played by the SNS on cancer biology has been largely encouraged.…”