Autonomic nerve development contributes to prostate cancer progression.

Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, Frenette PS
Science. 2013 341 (6142): 1236361

PMID: 23846904 · DOI:10.1126/science.1236361

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.

MeSH Terms (21)

Adenocarcinoma Adrenergic Fibers Animals Autonomic Nervous System Cell Line, Tumor Cell Transformation, Neoplastic Cholinergic Fibers Disease Progression Genes, myc Humans Male Mice Mice, Transgenic Neoplasm Invasiveness Neoplasm Transplantation Nerve Net Neurogenesis Parasympathetic Nervous System Promoter Regions, Genetic Prostate Prostatic Neoplasms

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