The Ependymal Region Prevents Glioblastoma From Penetrating Into the Ventricle via a Nonmechanical Force

作者：Kaishu Li, Haimin Song, Chaohu Wang, Zhiying Lin, Guozhong Yi, Runwei Yang, Bowen Ni, Ziyu Wang, Taichen Zhu, Wanghao Zhang, Xiran Wang, Zhifeng Liu, Guanglong Huang, Yawei Liu · 发表于：Frontiers in Neuroanatomy · 年份：2021 · DOI：10.3389/fnana.2021.679405 · 被引用次数：19 · 研究领域：Glioma Diagnosis and Treatment、Neurogenesis and neuroplasticity mechanisms、Cerebrospinal fluid and hydrocephalus

Background Intraventricular penetration is rare in glioblastoma (GBM). Whether the ependymal region including the ependyma and subventricular zone (SVZ) can prevent GBM invasion remains unclear. Methods Magnetic resonance imaging (MRI) and haematoxylin–eosin (HE) staining were performed to evaluate the size and anatomical locations of GBM. Binary logistic regression analysis was used to assess the correlation between tumor-ependyma contact, ventricle penetration and clinical characteristics. Cell migration and invasion were assessed via Transwell assays and an orthotopic transplantation model. Results Among 357 patients with GBM, the majority (66%) showed ependymal region contact, and 34 patients (10%) showed ventricle penetration of GBM. GBM cells were spread along the ependyma in the orthotopic transplantation model. The longest tumor diameter was an independent risk factor for GBM-ependymal region contact, as demonstrated by univariate (OR = 1.706, p < 0.0001) and multivariate logistic regression analyses (OR = 1.767, p < 0.0001), but was not associated with ventricle penetration. Cerebrospinal fluid (CSF) could significantly induce tumor cell migration ( p < 0.0001), and GBM could grow in CSF. Compared with those from the cortex, cells from the ependymal region attenuated the invasion of C6 whether cocultured with C6 or mixed with Matrigel ( p = 0.0054 and p = 0.0488). Immunofluorescence analysis shows a thin gap with GFAP expression delimiting the tu...