Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells

da Silva Barbara; Irving Bronwyn K.; Polson Euan S.; Droop Alastair; Griffiths Hollie B. S.; Mathew Ryan K.; Stead Lucy F.; Marrison Joanne; Williams Courtney; Williams Jennifer; Short Susan C.; Scarcia Margherita; OToole Peter J.; Allison Simon J.; Mavria Georgia; Wurdak Heiko

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Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells

机译：化学诱导的神经沸石异常揭示患者衍生的胶质母细胞瘤细胞中的多细胞网络功能

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Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo-induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.

机译：肿瘤干细胞和恶性多细胞网络已分别涉及胶质母细胞瘤的治疗耐药性（GBM），成人中最具侵袭性的脑癌。在此，我们表明R ROO相关的丝氨酸/苏氨酸激酶蛋白（ROCKI）的小分子抑制显着促进了非均相患者衍生的GBM干燥状细胞培养物中神经沸石样细胞突起的生长。这些投影形成了DE Novo诱导的蜂窝网络（INET）'腹板'，在Rocki撤离后回归。 INET网内的连接细胞显示出远程CA2 +信号传递，以及显着的溶酶体和线粒体贩运。与其较低的车辆控制对应物相比，在高剂量辐射后，INET细胞保持可行和增殖性。这些发现表明了岩石调节电池投影动力学和抗辐射多细胞网络的形成之间的联系。我们的研究确定了可逆地诱导INET WebS前体内的手段，从而可以将未来的研究加速到GBM蜂窝网络的生物学中。

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《Journal of Cell Science》 |2019年第19期|共10页
作者
da Silva Barbara; Irving Bronwyn K.; Polson Euan S.; Droop Alastair; Griffiths Hollie B. S.; Mathew Ryan K.; Stead Lucy F.; Marrison Joanne; Williams Courtney; Williams Jennifer; Short Susan C.; Scarcia Margherita; OToole Peter J.; Allison Simon J.; Mavria Georgia; Wurdak Heiko;
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作者单位

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Huddersfield Sch Appl Sci Huddersfield HD1 3DH W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ York Dept Biol York YO10 5DD N Yorkshire England;

Univ Huddersfield Sch Appl Sci Huddersfield HD1 3DH W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ York Dept Biol York YO10 5DD N Yorkshire England;

Univ Huddersfield Sch Appl Sci Huddersfield HD1 3DH W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

Univ Leeds Sch Med Leeds LS2 9JT W Yorkshire England;

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原文格式 PDF
正文语种 eng
中图分类细胞生物学;
关键词
Brain tumor; Glioblastoma multiforme; Patient-derived tumor cells; GBM stem-like cells; ROCK inhibition; Neurite-like outgrowth; Malignant multicellular network; Mitochondrial trafficking; Radiation resistance;

机译：脑肿瘤;胶质母细胞瘤多形状;患者衍生的肿瘤细胞;GBM干细胞;岩石抑制;神经沸石的过度;恶性多细胞网络;线粒体贩运;抗辐射抵抗;

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专利

1. Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells [J] . da Silva Barbara, Irving Bronwyn K., Polson Euan S., Journal of Cell Science . 2019,第19期

机译：化学诱导的神经沸石异常揭示患者衍生的胶质母细胞瘤细胞中的多细胞网络功能
2. Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens [J] . Pedron Sara, Wolter Gabrielle L., Chen Jee-Wei E., Biomaterials . 2019,第期

机译：透明质酸 - 官能化明胶水凝胶揭示了细胞外基质信号调味厄洛替尼对患者衍生的胶质母细胞瘤样品的功效
3. Proteomic profiling revealed the functional networks associated with mitotic catastrophe of HepG2 hepatoma cells induced by 6-bromine-5-hydroxy-4-methoxybenzaldehyde. [J] . Zhang B, Huang B, Guan H, Toxicology and Applied Pharmacology . 2011,第3期

机译：蛋白质组学分析揭示了与6-溴-5-羟基-4-羟基甲氧基苯甲醛诱导的HepG2肝癌细胞有丝分裂灾难有关的功能网络。
4. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells [C] . Nikola S. Mueller, Jan Krumsiek, Fabian J. Theis, Independent component analyses, wavelets, neural networks, biosystems, and nanoengineering IX . 2011

机译：高斯图形建模揭示胶质母细胞瘤细胞中特定的脂质相关性
5. Characterizing and Establishing Effects of L1CAM on Patient-Derived Glioblastoma Stem Cells [D] . Hellmig, Tyler. 2020

机译：L1CAM对患者衍生胶质母细胞瘤干细胞的特征和建立效果
6. Chemical ROCK inhibition induces neurite-like outgrowth and connectivity in undifferentiated glioblastoma cells [O] . Ms Bárbara da Silva, Dr Euan Polson, Dr Georgia Mavria, 2018

机译：化学ROCK抑制在未分化的胶质母细胞瘤细胞中诱导神经突样生长和连接
7. Chemically-induced Neurite-like Outgrowth Reveals Multicellular Network Function in Patient-derived Glioblastoma Cells [O] . Barbara da Silva, Euan S. Polson, Alastair Droop, 2018

机译：化学诱导的神经突状的过度揭示患者衍生的胶质母细胞瘤细胞中的多细胞网络功能

Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells

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