Autonomic nerve development contributes to prostate cancer progression

Claire Magnon, Simon J. Hall, Juan Lin, Xiaonan (Nan) Xue, Leah Gerber, Stephen J. Freedland, Paul S. Frenette

Research output: Contribution to journalArticle

338 Citations (Scopus)

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 b2- and b3-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.

Original languageEnglish (US)
Article number1236361
JournalScience
Volume341
Issue number6142
DOIs
StatePublished - 2013

Fingerprint

Autonomic Pathways
Prostatic Neoplasms
Neoplasms
Nerve Fibers
Prostate
Cholinergic Fibers
Sympathectomy
Muscarinic Receptors
Adrenergic Receptors
Cholinergic Agents
Adenocarcinoma
Pharmacology
Neoplasm Metastasis
Growth

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Autonomic nerve development contributes to prostate cancer progression. / Magnon, Claire; Hall, Simon J.; Lin, Juan; Xue, Xiaonan (Nan); Gerber, Leah; Freedland, Stephen J.; Frenette, Paul S.

In: Science, Vol. 341, No. 6142, 1236361, 2013.

Research output: Contribution to journalArticle

Magnon, Claire ; Hall, Simon J. ; Lin, Juan ; Xue, Xiaonan (Nan) ; Gerber, Leah ; Freedland, Stephen J. ; Frenette, Paul S. / Autonomic nerve development contributes to prostate cancer progression. In: Science. 2013 ; Vol. 341, No. 6142.
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