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脑肿瘤浸润边缘处小胶质细胞和神经胶质瘤细胞迁移的比较动力学研究。

Comparative dynamics of microglial and glioma cell motility at the infiltrative margin of brain tumours.

机构信息

Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.

出版信息

J R Soc Interface. 2018 Feb;15(139). doi: 10.1098/rsif.2017.0582.

Abstract

Microglia are a major cellular component of gliomas, and abundant in the centre of the tumour and at the infiltrative margins. While glioma is a notoriously infiltrative disease, the dynamics of microglia and glioma migratory patterns have not been well characterized. To investigate the migratory behaviour of microglia and glioma cells at the infiltrative edge, we performed two-colour time-lapse fluorescence microscopy of brain slices generated from a platelet-derived growth factor-B (PDGFB)-driven rat model of glioma, in which glioma cells and microglia were each labelled with one of two different fluorescent markers. We used mathematical techniques to analyse glioma cells and microglia motility with both single cell tracking and particle image velocimetry (PIV). Our results show microglia motility is strongly correlated with the presence of glioma, while the correlation of the speeds of glioma cells and microglia was variable and weak. Additionally, we showed that microglia and glioma cells exhibit different types of diffusive migratory behaviour. Microglia movement fit a simple random walk, while glioma cell movement fits a super diffusion pattern. These results show that glioma cells stimulate microglia motility at the infiltrative margins, creating a correlation between the spatial distribution of glioma cells and the pattern of microglia motility.

摘要

小胶质细胞是神经胶质瘤的主要细胞成分,大量存在于肿瘤中心和浸润边缘。虽然神经胶质瘤是一种众所周知的浸润性疾病,但小胶质细胞和神经胶质瘤迁移模式的动力学尚未得到很好的描述。为了研究浸润边缘中小胶质细胞和神经胶质瘤细胞的迁移行为,我们对源自血小板衍生生长因子-B(PDGFB)驱动的大鼠神经胶质瘤模型的脑切片进行了双色延时荧光显微镜观察,其中神经胶质瘤细胞和小胶质细胞分别用两种不同荧光标记物之一进行标记。我们使用数学技术通过单细胞跟踪和粒子图像测速(PIV)来分析神经胶质瘤细胞和小胶质细胞的运动。我们的结果表明,小胶质细胞的运动与神经胶质瘤的存在密切相关,而神经胶质瘤细胞和小胶质细胞的速度相关性则是可变的且较弱。此外,我们还表明,小胶质细胞和神经胶质瘤细胞表现出不同类型的扩散迁移行为。小胶质细胞的运动符合简单的随机游走,而神经胶质瘤细胞的运动符合超扩散模式。这些结果表明,神经胶质瘤细胞在浸润边缘刺激小胶质细胞运动,从而在神经胶质瘤细胞的空间分布和小胶质细胞运动模式之间产生相关性。

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