Cancer-Related Axonogenesis and Neurogenesis in Prostate Cancer
Cancer-Related Axonogenesis and Neurogenesis in Prostate Cancer
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DOI：
10.1158/1078-0432.ccr-08-1164
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发表时间：
2008-12-01
影响因子：
11.5
通讯作者：
Rowley, David
中科院分区：
文献类型：
--
作者：
Ayala, Gustavo E.;Dai, Hong;Rowley, David
目的：神经侵袭是迄今为止研究的唯一肿瘤细胞与神经之间的相互作用。癌症和神经之间的共生关系为两者带来了生长优势。在这篇文章中，我们提供了一种新的生物学现象，癌症相关的轴突发生和神经发生的数据。实验设计：我们确定神经密度增加与人类前列腺癌前病变和肿瘤性病变之间的空间和时间联系。结果：与对照相比，癌区域和癌前病变中神经密度增加。对整个前列腺的二维和三维重建证实了人类肿瘤中的轴突发生。此外，与对照组相比，前列腺癌患者前列腺神经节中的神经元数量增加，这证实了神经发生。最后，两个体外模型证实，在前列腺癌中，癌细胞，特别是在与神经相互作用时，在神经周围侵袭时，会诱导轴突生长。神经发生与侵袭性前列腺癌的特征和前列腺癌的复发有关。我们还提出了一种基于信号素4F(S4F)的可能的调控机制。在体外神经周模型中，S4F在癌细胞中过表达。在N1E-115神经发生实验中，S4F在前列腺癌细胞中过表达可诱导神经发生，而小干扰RNA抑制S4F可阻断这一作用。结论：这是首次描述与肿瘤相关的神经发生及其可能的调控机制。
Purpose: Perineural invasion is the only interaction between cancer cells and nerves studied to date. It is a symbiotic relationship between cancer and nerves that results in growth advantage for both. In this article, we present data on a novel biological phenomenon, cancer-related axonogenesis and neurogenesis.Experimental Design: We identify spatial and temporal associations between increased nerve density and preneoplastic and neoplastic lesions of the human prostate.Results: Nerve density was increased in cancer areas as well as in preneoplastic lesions compared with controls. Two- and three-dimensional reconstructions of entire prostates confirmed axonogenesis in human tumors. Furthermore, patients with prostate cancer had increased numbers of neurons in their prostatic ganglia compared with controls, corroborating neurogenesis. Finally, two in vitro models confirmed that cancer cells, particularly when interacting with nerves in perineural invasion, induce neurite outgrowth in prostate cancer. Neurogenesis is correlated with features of aggressive prostate cancer and with recurrence in prostate cancer. We also present a putative regulatory mechanism based on semaphorin 4F (S4F). S4F is overexpressed in cancers cells in the perineural in vitro model. Overexpression of S4F in prostate cancer cells induces neurogenesis in the N1E-115 neurogenesis assay and S4F inhibition by small interfering RNA blocks this effect.Conclusions: This is the first description of cancer-related neurogenesis and its putative regulatory mechanism.