Autonomic nerve development contributes to prostate cancer progression.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Magnon, C; Hall, SJ; Lin, J; Xue, X; Gerber, L; Freedland, SJ; Frenette, PS

Published Date

  • July 2013

Published In

Volume / Issue

  • 341 / 6142

Start / End Page

  • 1236361 -

PubMed ID

  • 23846904

Pubmed Central ID

  • 23846904

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1236361

Language

  • eng