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首页> 外文期刊>Biophysical Journal >Glioma Cell Migration Dynamics in Brain Tissue Assessed by Multimodal Optical Imaging
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Glioma Cell Migration Dynamics in Brain Tissue Assessed by Multimodal Optical Imaging

机译：多式光学成像评估脑组织中的胶质瘤细胞迁移动态

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Glioblastoma is a primary malignant brain tumor characterized by highly infiltrative glioma cells. Vasculature and white matter tracts are considered to be the preferred and fastest routes for glioma invasion through brain tissue. In this study, we systematically quantified the routes and motility of the U251 human glioblastoma cell line in mouse brain slices by multimodal imaging. Specifically, we used polarization-sensitive optical coherence tomography to delineate nerve fiber tracts while confocal fluorescence microscopy was used to image cell migration and brain vasculature. Somewhat surprisingly, we found that in mouse brain slices, U251 glioma cells do not follow white matter tracts but rather preferentially migrate along vasculature in both gray and white matter. In addition, U251 cell motility is similar to 2-fold higher in gray matter than in white matter (91 vs. 43 mu m(2)/h), with a substantial fraction (44%) of cells in both regions invading without close association with vasculature. Interestingly, within both regions, the rates of migration for the perivascular and televascular routes of invasion were indistinguishable. Furthermore, by imaging of local vasculature deformation dynamics during cell migration, we found that U251 cells are capable of exerting traction forces that locally pull on their environment, suggesting the applicability of a "motor-clutch"-based model for migration in vivo. Overall, by quantitatively analyzing the migration dynamics along the diverse pathways followed by invading U251 glioma cells as observed by our multimodal imaging approach, our studies suggest that effective antiinvasive strategies will need to simultaneously limit parallel routes of both perivascular and televascular invasion through both gray and white matter.
机译：胶质母细胞瘤是一种主要恶性脑肿瘤，其特征是高度渗透性胶质瘤细胞。脉管系统和白质散布被认为是脑组织脑组织的优选和最快的胶质瘤侵袭途径。在本研究中，通过多式联成像系统地量化了U251人胶质母细胞瘤细胞中U251人胶质母细胞瘤细胞系的途径和动力。具体地，我们使用偏振敏感光学相干断层扫描来描绘神经纤维束，同时共聚焦荧光显微镜用于图像细胞迁移和脑脉管系统。有些令人惊讶的是，我们发现在小鼠脑切片中，U251胶质瘤细胞不遵循白质散布，而是沿灰色和白质沿脉管系统迁移。此外，U251细胞运动与灰色物质中的2倍相似，而不是白体（91与43μm（2）/ h），在没有接近的情况下，两个地区的侵入中具有大量分数（44％）细胞与脉管系统联系。有趣的是，在两个地区，血管外和临时入侵途径的迁移率都无法区分。此外，通过在细胞迁移期间成像局部脉管系统变形动态，我们发现U251细胞能够施加局部拉动其环境的牵引力，这表明在体内迁移的“电动离合器”基础模型的适用性。总体而言，通过定量分析沿着多种途径的不同途径分析迁移动态，然后通过我们的多式联数成像方法观察到侵入U251胶质瘤细胞，我们的研究表明，有效的抗冒险策略需要通过灰色和白质。

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