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Publication : Autonomic nerve development contributes to prostate cancer progression.

First Author  Magnon C Year  2013
Journal  Science Volume  341
Issue  6142 Pages  1236361
PubMed ID  23846904 Mgi Jnum  J:199439
Mgi Id  MGI:5502791 Doi  10.1126/science.1236361
Citation  Magnon C, et al. (2013) Autonomic nerve development contributes to prostate cancer progression. Science 341(6142):1236361
abstractText  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 beta2- and beta3-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.
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