Time-lapse phenotyping of invasive glioma cells ex vivo reveals subtype-specific movement patterns guided by tumor core signaling
Time-lapse phenotyping of invasive glioma cells ex vivo reveals subtype-specific movement patterns guided by tumor core signaling
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DOI：
10.1016/j.yexcr.2016.08.001
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发表时间：
2016-12-10
影响因子：
3.7
通讯作者：
Vik-Mo, Einar O.
中科院分区：
文献类型：
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作者：
Fayzullin, Artem;Tuvnes, Frode A.;Vik-Mo, Einar O.
胶质母细胞瘤侵袭的生物学特性及其机制目前知之甚少。我们使用时间推移显微镜证明，将胶质母细胞瘤(GBM)肿瘤球体移植到啮齿动物脑片中会导致实验性的体外肿瘤，其侵袭性与原位移植到啮齿动物大脑中后观察到的侵袭性基本相同。迁移运动和有丝分裂模式明显地被入侵细胞外部的信号所改变。细胞从肿瘤球体中移开，去除肿瘤球体减少了定向侵袭运动。培养的细胞含有不同群体的侵袭细胞，具有不同的形态和侵袭行为模式。最具侵袭性的GBM培养的移植物含有91+/-8%的细胞，具有侵袭性表型，其特点是胞体小，具有明显的前导突起。相反，在侵袭性较小的GBM移植物中，大多数细胞是表型异质性的：只有6.3+/-4.1%的细胞具有侵袭性表型。在观察期间，高侵袭和中等侵袭培养的移植物有不同比例的细胞进入脑片实质：分别为89.2+/-2.2%和23.1+/-6.8%。在中等侵袭性的移植物中，大多数侵袭周围脑组织的细胞(76.8+/-6.8%)返回肿瘤体积或停止离心性迁移。我们的数据表明，单个GBM肿瘤的侵袭性可以由具有特定侵袭形态的细胞比例以及肿瘤核心和侵袭性细胞之间的信号转导来调节。这些发现对于开发针对侵袭性GBM细胞的新的治疗策略具有重要意义。(C)2016年提交人。由爱思唯尔公司出版。
The biology of glioblastoma invasion and its mechanisms are poorly understood. We demonstrate using time-lapse microscopy that grafting of glioblastoma (GBM) tumorspheres into rodent brain slices results in experimental ex vivo tumors with invasive properties that recapitulate the invasion observed after orthotopic transplantation into the rodent brain.The migratory movements and mitotic patterns were clearly modified by signals extrinsic to the invading cells. The cells migrated away from the tumorspheres, and removal of the spheres reduced the directed invasive movement. The cell cultures contained different populations of invasive cells that had distinct morphology and invasive behavior patterns. Grafts of the most invasive GBM culture contained 91 +/- 8% cells with an invasive phenotype, characterized by small soma with a distinct leading process. Conversely, the majority of cells in less invasive GBM grafts were phenotypically heterogeneous: only 6.3 +/- 4.1% of the cells had the invasive phenotype. Grafts of highly and moderately invasive cultures had different proportions of cells that advanced into the brain slice parenchyma during the observation period: 89.2 +/- 2.2% and 23.1 +/- 6.8%, respectively. In grafts with moderately invasive properties, most of the cells (76.8 +/- 6.8%) invading the surrounding brain tissue returned to the tumor bulk or stopped centrifugal migration.Our data suggest that the invasion of individual GBM tumors can be conditioned by the prevalence of a cell fraction with particular invasive morphology and by signaling between the tumor core and invasive cells. These findings can be important for the development of new therapeutic strategies that target the invasive GBM cells. (C) 2016 The Authors. Published by Elsevier Inc.