Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma.
Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma.
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DOI：
10.1007/s00418-017-1604-2
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发表时间：
2017-10
影响因子：
2.3
通讯作者：
Friedl P
中科院分区：
文献类型：
--
作者：
Gritsenko P;Leenders W;Friedl P
胶质瘤细胞向脑实质的扩散性侵袭导致脑肿瘤不能切除，胶质瘤疾病预后差。在体内，神经胶质瘤细胞可以通过作为单细胞、聚集链和多细胞网络沿着血管周围、神经元周围和间质引导线索移动来采取一系列侵袭策略和途径。然而，目前在体外检测，以探测胶质瘤细胞的侵袭，是有限的，在概括的模式和适应性胶质瘤的侵袭在脑实质中观察到的，包括集体行为。为了在体外模拟体内胶质瘤细胞的侵袭，我们在这里应用了三种组织启发的3D环境，结合多细胞胶质瘤球体和血管和间质脑结构的重建显微解剖特征。使用（1）代表沿着脑血管的空间的重建基底膜/透明质酸界面;（2）由多层小鼠星形胶质细胞产生的3D支架以反映脑胶质细胞;和（3）离体新鲜分离的小鼠脑切片培养物，监测人细胞系和患者来源的异种移植细胞的多细胞胶质瘤球体的径向迁移。使用来自胶质母细胞瘤患者和浸润小鼠脑的胶质瘤异种移植物的脑切片的组织学分析来验证体外侵袭模式。每个3D分析都概括了在小鼠异种移植物和患者脑样品中鉴定的主要胶质瘤侵袭模式的不同方面，包括单独迁移的细胞，沿着血管延伸的集体链，以及浸润神经胶质瘤的互连胶质瘤细胞的多细胞网络。结合，这些器官型测定使胶质瘤细胞使用的一系列侵袭模式成为可能，并将适用于胶质瘤细胞播散的机制分析和靶向。
Diffuse invasion of glioma cells into the brain parenchyma leads to nonresectable brain tumors and poor prognosis of glioma disease. In vivo, glioma cells can adopt a range of invasion strategies and routes, by moving as single cells, collective strands and multicellular networks along perivascular, perineuronal and interstitial guidance cues. Current in vitro assays to probe glioma cell invasion, however, are limited in recapitulating the modes and adaptability of glioma invasion observed in brain parenchyma, including collective behaviours. To mimic in vivo-like glioma cell invasion in vitro, we here applied three tissue-inspired 3D environments combining multicellular glioma spheroids and reconstituted microanatomic features of vascular and interstitial brain structures. Radial migration from multicellular glioma spheroids of human cell lines and patient-derived xenograft cells was monitored using (1) reconstituted basement membrane/hyaluronan interfaces representing the space along brain vessels; (2) 3D scaffolds generated by multi-layered mouse astrocytes to reflect brain interstitium; and (3) freshly isolated mouse brain slice culture ex vivo. The invasion patterns in vitro were validated using histological analysis of brain sections from glioblastoma patients and glioma xenografts infiltrating the mouse brain. Each 3D assay recapitulated distinct aspects of major glioma invasion patterns identified in mouse xenografts and patient brain samples, including individually migrating cells, collective strands extending along blood vessels, and multicellular networks of interconnected glioma cells infiltrating the neuropil. In conjunction, these organotypic assays enable a range of invasion modes used by glioma cells and will be applicable for mechanistic analysis and targeting of glioma cell dissemination.
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影响因子：
4.6
作者：
Frolov A;Evans IM;Li N;Sidlauskas K;Paliashvili K;Lockwood N;Barrett A;Brandner S;Zachary IC;Frankel P
通讯作者：
Frankel P
影响因子：
16.6
作者：
Bangasser BL;Shamsan GA;Chan CE;Opoku KN;Tüzel E;Schlichtmann BW;Kasim JA;Fuller BJ;McCullough BR;Rosenfeld SS;Odde DJ
通讯作者：
Odde DJ
影响因子：
3.7
作者：
Fayzullin, Artem;Tuvnes, Frode A.;Vik-Mo, Einar O.
通讯作者：
Vik-Mo, Einar O.
影响因子：
--
作者：
Hong X;Sin WC;Harris AL;Naus CC
通讯作者：
Naus CC
影响因子：
14
作者：
Ananthanarayanan, Badriprasad;Kim, Yushan;Kumar, Sanjay
通讯作者：
Kumar, Sanjay