Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Science. 2013 Jul 12;341(6142):1236361. doi: 10.1126/science.1236361.
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.
神经是微环境的一个共同特征，但它们在肿瘤生长和进展中的作用仍不清楚。我们发现，前列腺中自主神经纤维的形成调节着前列腺癌在小鼠模型中的发展和扩散。通过化学或手术交感神经切除术以及基质β2-和β3-肾上腺素能受体的基因缺失，早期肿瘤发展被阻止。肿瘤也被副交感胆碱能纤维浸润，促进癌症扩散。通过药理学阻断或基质型 1 毒蕈碱受体的基因破坏，抑制胆碱能诱导的肿瘤侵袭和转移，从而提高小鼠的存活率。对 43 名前列腺腺癌患者的前列腺腺癌标本进行的回顾性盲法分析显示，肿瘤和周围正常组织中交感和副交感神经纤维的密度分别与不良的临床结局相关。这些发现可能为前列腺癌提供新的治疗方法。
