Publication Date:
2013-07-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Magnon, Claire -- Hall, Simon J -- Lin, Juan -- Xue, Xiaonan -- Gerber, Leah -- Freedland, Stephen J -- Frenette, Paul S -- DK056638/DK/NIDDK NIH HHS/ -- HL069438/HL/NHLBI NIH HHS/ -- HL097819/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 12;341(6142):1236361. doi: 10.1126/science.1236361.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846904" target="_blank"〉PubMed〈/a〉
Keywords:
Adenocarcinoma/*pathology
;
Adrenergic Fibers/physiology
;
Animals
;
Autonomic Nervous System/*growth & development
;
Cell Line, Tumor
;
Cell Transformation, Neoplastic/pathology
;
Cholinergic Fibers/physiology
;
Disease Progression
;
Genes, myc/genetics
;
Humans
;
Male
;
Mice
;
Mice, Transgenic
;
Neoplasm Invasiveness
;
Neoplasm Transplantation
;
Nerve Net/pathology/physiology
;
*Neurogenesis
;
Parasympathetic Nervous System/growth & development
;
Promoter Regions, Genetic
;
Prostate/*innervation/*pathology
;
Prostatic Neoplasms/*pathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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