小柯机器人

近日，德国海德堡大学医院Frank Winkler等研究人员合作发现胶质母细胞瘤劫持脑侵袭的神经机制。2022年7月31日，《细胞》杂志在线发表了这项成果。

研究人员证明了全脑定植是由胶质母细胞瘤细胞推动的，这些细胞缺乏与其他肿瘤细胞和星形胶质细胞的连接，但却接受神经元的突触输入。这个亚群对应于神经元和神经祖细胞样的肿瘤细胞状态，这是由单细胞转录组学定义的，在小鼠模型和人类疾病中都是如此。肿瘤细胞的入侵类似于神经元的迁移机制，并采用了类似Lévy的运动模式来探测环境。神经元活动在胶质母细胞瘤细胞中诱发了复杂的钙信号，随后肿瘤微管（TM）从新形成并增加了入侵速度。

总之，分子和功能单细胞数据的叠加显示，神经元机制在多个层面上支配着胶质母细胞瘤细胞的侵袭。这解释了胶质母细胞瘤的扩散和细胞的异质性是如何紧密联系在一起的。

据介绍，胶质母细胞瘤是浸润在大脑中的无法治愈的肿瘤。胶质母细胞瘤细胞的一个亚群形成了一个由TM相互连接的功能性和抗治疗的肿瘤细胞网络。其他亚群似乎没有联系，它们的生物学作用仍不清楚。

附：英文原文

Title: Glioblastoma hijacks neuronal mechanisms for brain invasion

Author: Varun Venkataramani, Yvonne Yang, Marc Cicero Schubert, Ekin Reyhan, Svenja Kristin Tetzlaff, Niklas Wimann, Michael Botz, Stella Judith Soyka, Carlo Antonio Beretta, Rangel Lyubomirov Pramatarov, Laura Fankhauser, Luciano Garofano, Alexander Freudenberg, Julia Wagner, Dimitar Ivanov Tanev, Miriam Ratliff, Ruifan Xie, Tobias Kessler, Dirk C. Hoffmann, Ling Hai, Yvette Drflinger, Simone Hoppe, Yahaya A. Yabo, Anna Golebiewska, Simone P. Niclou, Felix Sahm, Anna Lasorella, Martin Slowik, Leif Dring, Antonio Iavarone, Wolfgang Wick, Thomas Kuner, Frank Winkler

Issue&Volume: 2022-07-31

Abstract: Glioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other subpopulations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease. Tumor cell invasion resembled neuronal migration mechanisms and adopted a Lévy-like movement pattern of probing the environment. Neuronal activity induced complex calcium signals in glioblastoma cells followed by the de novo formation of TMs and increased invasion speed. Collectively, superimposing molecular and functional single-cell data revealed that neuronal mechanisms govern glioblastoma cell invasion on multiple levels. This explains how glioblastoma’s dissemination and cellular heterogeneity are closely interlinked.

DOI: 10.1016/j.cell.2022.06.054

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00847-9