小柯机器人

研究揭示谷氨酸能突触输入驱动脑肿瘤进展
2019-09-19 15:22

德国海德堡大学Thomas Kuner和Varun Venkataramani团队合作发现了神经胶质瘤细胞的谷氨酸能突触输入驱动脑肿瘤的进展。该成果于2019年9月18日在线发表于《自然》。

研究团队发现了不同疾病模型和人类肿瘤中神经元和神经胶质瘤细胞之间的直接沟通渠道,突触前神经元和突触后神经胶质瘤细胞之间的真正的功能性化学信号突触。这些神经胶质突触显示位于肿瘤微管上典型的突触超微结构,并产生由AMPA亚型的谷氨酸受体介导的突触后电流。包括癫痫病症在内的神经元活动在肿瘤-微管连接的神经胶质瘤网络中产生同步的钙瞬变。AMPA受体的胶质瘤细胞特异性遗传扰动降低了肿瘤微管阳性肿瘤细胞和胶质瘤生长的钙相关侵袭。麻醉和AMPA受体拮抗剂perampanel也分别减少了侵袭和生长。这些发现揭示了神经元和神经胶质瘤细胞之间生物学相关的直接突触通信,具有潜在的临床意义。

据了解,由肿瘤微管连接的通信肿瘤细胞网络介导无法治愈的神经胶质瘤的进展。此外,神经元活动可通过非突触旁分泌和自分泌机制促进胶质瘤细胞的恶化。

附:英文原文

Title: Glutamatergic synaptic input to glioma cells drives brain tumour progression

Author: Varun Venkataramani, Dimitar Ivanov Tanev, Christopher Strahle, Alexander Studier-Fischer, Laura Fankhauser, Tobias Kessler, Christoph Krber, Markus Kardorff, Miriam Ratliff, Ruifan Xie, Heinz Horstmann, Mirko Messer, Sang Peter Paik, Johannes Knabbe, Felix Sahm, Felix T. Kurz, Azer Aylin Acikgz, Frank Herrmannsdrfer, Amit Agarwal, Dwight E. Bergles, Anthony Chalmers, Hrvoje Miletic, Sevin Turcan, Christian Mawrin, Daniel Hnggi, Hai-Kun Liu, Wolfgang Wick, Frank Winkler, Thomas Kuner

Issue&Volume: 2019-09-18

Abstract: 

A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.

DOI: 10.1038/s41586-019-1564-x

Source:https://www.nature.com/articles/s41586-019-1564-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
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

分享到:

0