Transplanted glioma cells migrate and proliferate on host brain vasculature: A dynamic analysis
Transplanted glioma cells migrate and proliferate on host brain vasculature: A dynamic analysis
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作者：
Farin, A;Suzuki, SO;Canoll, P
神经胶质瘤细胞具有显著的能力，可以浸润大脑并从肿瘤长距离迁移，使得完全的手术切除变得不可能。然而，人们对胶质瘤细胞如何与大脑复杂的微环境相互作用知之甚少。为了研究胶质瘤细胞浸润和迁移的模式和动力学，我们将eGFP和DsRed-2标记的大鼠C6胶质瘤细胞立体定向注射到新生大鼠前脑中，并使用延时显微镜观察胶质瘤细胞在这些大脑产生的切片培养物中的迁移和增殖。在该模型中，胶质瘤细胞通过沿着血管的近腔表面迁移而广泛地浸润脑。胶质瘤细胞在血管内皮细胞和血管周围星形胶质细胞端足之间插入其突起，但不侵入血管腔。动态分析显示，胶质瘤细胞的迁移行为和以前观察到的胶质祖细胞之间的显着相似之处。胶质瘤细胞有一个特征性的前导过程，并以跳跃式的方式迁移，迁移的爆发被不动期所分隔，最大速度超过100 μ m/h。迁移的神经胶质瘤细胞在途中增殖，在子细胞恢复迁移之前暂停一个小时进行分裂。值得注意的是，大多数神经胶质瘤细胞分裂发生在或接近血管分支点，这表明有丝分裂是由局部环境因素触发的。这项研究提供了胶质瘤细胞浸润在活体脑组织中的第一个动态分析，并揭示了移植的胶质瘤细胞的迁移和增殖是由与宿主脑血管系统的相互作用指导的。(c)2006 Wiley-Liss，Inc.
Glioma cells have a remarkable capacity to infiltrate the brain and migrate long distances from the tumor, making complete surgical resection impossible. Yet, little is known about how glioma cells interact with the complex microenvironment of the brain. To investigate the patterns and dynamics of glioma cell infiltration and migration, we stereotactically injected eGFP and DsRed-2 labeled rat C6 glioma cells into neonatal rat forebrains and used time-lapse microscopy to observe glioma cell migration and proliferation in slice cultures generated from these brains. In this model, glioma cells extensively infiltrated the brain by migrating along the abluminal surface of blood vessels. Glioma cells intercalated their processes between the endothelial cells and the perivascular astrocyte end feet, but did not invade into the blood vessel lumen. Dynamic analysis revealed notable similarities between the migratory behavior of glioma cells and that previously observed for glial progenitor cells. Glioma cells had a characteristic leading process and migrated in a saltatory fashion, with bursts of migration separated by periods of immobility, and maximum speeds of over 100 mu m/h. Migrating glioma cells proliferated en route, pausing for as short as an hour to divide before the daughter cells resumed migrating. Remarkably, the majority of glioma cell divisions took place at or near vascular branch points, suggesting that mitosis is triggered by local environmental cues. This study provides the first dynamic analysis of glioma cell infiltration in living brain tissue and reveals that the migration and proliferation of transplanted glioma cells is directed by interactions with host brain vasculature. (c) 2006 Wiley-Liss, Inc.