Autonomic Nerve Development Contributes to Prostate Cancer Progression
Top Cited Papers
- 12 July 2013
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 341 (6142), 1236361
- https://doi.org/10.1126/science.1236361
Abstract
Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.Keywords
This publication has 35 references indexed in Scilit:
- Use of β‐blockers is associated with prostate cancer‐specific survival in prostate cancer patients on androgen deprivation therapyThe Prostate, 2012
- Radical Prostatectomy versus Observation for Localized Prostate CancerThe New England Journal of Medicine, 2012
- Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for interventionCarcinogenesis: Integrative Cancer Research, 2011
- β-Blockers and Survival among Danish Patients with Malignant Melanoma: A Population-Based Cohort StudyCancer Epidemiology, Biomarkers & Prevention, 2011
- Beta-Blocker Use Is Associated With Improved Relapse-Free Survival in Patients With Triple-Negative Breast CancerJournal of Clinical Oncology, 2011
- Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injuryNature Medicine, 2009
- Stromal Antiapoptotic Paracrine Loop in Perineural Invasion of Prostatic CarcinomaCancer Research, 2006
- Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone MarrowCell, 2006
- Common mechanisms of nerve and blood vessel wiringNature, 2005
- Central oxotremorine antagonist properties of pirenzepineLife Sciences, 1988