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

The Ependymal Region Prevents Glioblastoma From Penetrating Into the Ventricle via a Nonmechanical Force.
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室管膜区域通过非机械力防止胶质母细胞瘤侵入心室

DOI:
10.3389/fnana.2021.679405
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发表时间:
2021
影响因子:
2.9
通讯作者:
Liu Y
Liu Y
中科院分区:
医学3区
文献类型:
--
作者:
Li K;Song H;Wang C;Lin Z;Yi G;Yang R;Ni B;Wang Z;Zhu T;Zhang W;Wang X;Liu Z;Huang G;Liu Y

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脑室内穿透在胶质母细胞瘤(GBM)中是罕见的。室管膜区(包括室管膜和室管膜下区(SVZ))是否可以防止GBM侵袭仍不清楚。磁共振成像(MRI)和苏木精-伊红(HE)染色,以评估GBM的大小和解剖位置。二元逻辑回归分析用于评估肿瘤-室管膜接触、脑室穿透与临床特征之间的相关性。通过Transwell测定和原位移植模型评估细胞迁移和侵袭。在357例GBM患者中,大多数(66%)显示室管膜区接触,34例(10%)显示GBM穿透心室。在原位移植模型中,GBM细胞沿着室管膜扩散。单变量(OR = 1.706,p < 0.0001)和多变量logistic回归分析(OR = 1.767,p <0.0001)表明,最长肿瘤直径是GBM-室管膜区域接触的独立风险因素,但与心室穿透无关。脑脊液(CSF)可明显诱导肿瘤细胞迁移(p < 0.0001),GBM可在CSF中生长。与来自皮质的细胞相比,来自室管膜区的细胞减弱了C6的侵袭,无论是与C6共培养还是与Matrigel混合培养(p = 0.0054和p = 0.0488)。免疫荧光分析显示肿瘤和室管膜区域有一个GFAP表达的薄间隙。室管膜区可能通过非机械力限制GBM细胞进入心室。这一领域的进一步研究可能揭示GBM患者中发生的机制,并可能设计新的治疗策略。
Intraventricular penetration is rare in glioblastoma (GBM). Whether the ependymal region including the ependyma and subventricular zone (SVZ) can prevent GBM invasion remains unclear. 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. 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 tumor and ependymal region. The ependymal region might restrict GBM cells from entering the ventricle via a non-mechanical force. Further studies in this area may reveal mechanisms that occur in GBM patients and may enable the design of new therapeutic strategies.
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