title: Autonomic nerve development contributes to prostate cancer progression.
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.
authors.affiliation: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA. clairemagnon@free.fr
authors.forename: Claire
authors.initials: C
authors.lastname: Magnon
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hall
authors.forename: Juan
authors.initials: J
authors.lastname: Lin
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000320:Adrenergic Fibers / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000254:growth & development*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002799:Cholinergic Fibers / Q000502:physiology; D018450:Disease Progression; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009415:Nerve Net / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis; D010275:Parasympathetic Nervous System / Q000254:growth & development; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000294:innervation* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*