瑞士洛桑联邦理工学院Douglas Hanahan课题组在研究中取得进展。他们发现临近突触能够激活NMDAR信号从而促进乳腺癌脑转移。该项研究成果在线发表于2019年9月18日的《自然》杂志上。
研究人员发现乳腺-脑转移（B2BM）细胞会共同选择一条神经元信号通路，最近发现其涉及侵入性肿瘤生长；这条通路涉及谷氨酸配体对N-甲基-D-天冬氨酸受体（NMDAR）的激活，这是转移性定植大脑模型的关键并与预后不良有关。尽管NMDAR激活在一些原发性肿瘤类型中是自分泌型的，人和小鼠B2BM细胞表达这些受体，但分泌的谷氨酸不足以诱导该信号，而是通过在癌细胞和谷氨酸能神经元之间形成假三方突触来实现，从而为脑转移提供理论依据。
研究人员表示，转移，即远处器官中肿瘤的播散性生长，是癌症死亡率的基础。B2BM是一种常见且具有破坏性的癌症形式，并且在侵袭性基底样亚型中普遍存在，在所有癌症亚型中也以不同频率存在。以前的研究揭示了乳腺癌转移到大脑的因素，但它对这个部位的偏好仍然是一个谜。
附：英文原文
Title: Synaptic proximity enables NMDAR signalling to promote brain metastasis
Author: Qiqun Zeng, Iacovos P. Michael, Peng Zhang, Sadegh Saghafinia, Graham Knott, Wei Jiao, Brian D. McCabe, Jos A. Galvn, Hugh P. C. Robinson, Inti Zlobec, Giovanni Ciriello, Douglas Hanahan
Issue&Volume: 2019-09-18
Abstract:
Metastasis—the disseminated growth of tumours in distant organs—underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the brain, but its preference for this site remains an enigma. Here we show that B2BM cells co-opt a neuronal signalling pathway that was recently implicated in invasive tumour growth, involving activation by glutamate ligands of N-methyl-D-aspartate receptors (NMDARs), which is key in model systems for metastatic colonization of the brain and is associated with poor prognosis. Whereas NMDAR activation is autocrine in some primary tumour types, human and mouse B2BM cells express receptors but secrete insufficient glutamate to induce signalling, which is instead achieved by the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons, presenting a rationale for brain metastasis.
DOI: 10.1038/s41586-019-1576-6
Source:https://www.nature.com/articles/s41586-019-1576-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
