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

Li, Kaishu; Song, Haimin; Wang, Chaohu; Lin, Zhiying; Yi, Guozhong; Yang, Run-Wei; Ni, Bowen; Wang, Ziyu; Zhu, Taichen; Zhang, Wanghao; Wang, Xiran; Liu, Zhifeng; Huang, Guanglong; Liu, Yawei

doi:10.3389/fnana.2021.679405

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…GBM cells extend processes to interact with the CSF and, occasionally, invade to occupy the LV ependymal cell surface. This is in opposition to previously published work, where researchers have found that the ependymal cell monolayer actively prevents GBM penetration into the ventricle [ 47 ]. Based on our findings, we propose that there are only small regional areas of ependymal cell disruption where invading cells are able to penetrate into the ventricular lumen, thereby affecting the biology of many nearby ependymal cells.…”

Section: Discussioncontrasting

confidence: 99%

Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone

Norton

Whaley

Ulloa-Navas

et al. 2022

Fluids Barriers CNS

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Background Glioblastoma (GBM) is the most aggressive and common type of primary brain tumor in adults. Tumor location plays a role in patient prognosis, with tumors proximal to the lateral ventricles (LVs) presenting with worse overall survival, increased expression of stem cell genes, and increased incidence of distal tumor recurrence. This may be due in part to interaction of GBM with factors of the subventricular zone (SVZ), including those contained within the cerebrospinal fluid (CSF). However, direct interaction of GBM tumors with CSF has not been proved and would be hindered in the presence of an intact ependymal cell layer. Methods Here, we investigate the ependymal cell barrier and its derived extracellular matrix (ECM) fractones in the vicinity of a GBM tumor. Patient-derived GBM cells were orthotopically implanted into immunosuppressed athymic mice in locations distal and proximal to the LV. A PBS vehicle injection in the proximal location was included as a control. At four weeks post-xenograft, brain tissue was examined for alterations in ependymal cell health via immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. Results We identified local invading GBM cells within the LV wall and increased influx of CSF into the LV-proximal GBM tumor bulk compared to controls. In addition to the physical disruption of the ependymal cell barrier, we also identified increased signs of compromised ependymal cell health in LV-proximal tumor-bearing mice. These signs include increased accumulation of lipid droplets, decreased cilia length and number, and decreased expression of cell channel proteins. We additionally identified elevated numbers of small fractones in the SVZ within this group, suggesting increased indirect CSF-contained molecule signaling to tumor cells. Conclusions Our data is the first to show that LV-proximal GBMs physically disrupt the ependymal cell barrier in animal models, resulting in disruptions in ependymal cell biology and increased CSF interaction with the tumor bulk. These findings point to ependymal cell health and CSF-contained molecules as potential axes for therapeutic targeting in the treatment of GBM.

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Section: Discussioncontrasting

confidence: 99%

Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone

Norton

Whaley

Ulloa-Navas

et al. 2022

Fluids Barriers CNS

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“…A recent study identified ependymal contact in the majority of glioblastomas (237/357, 66%), and observed ventricular invasion of the tumors in only 34/237 patients (14.3%). 25 The authors also found that tumor invasion into the ventricles was inhibited via a nonmechanical force in the ependymal region. 25 Notably, significant differences were observed in the survival prognosis of patients with DHGs-G34m showing ill-defined margins and those with DHGs-G34m showing well-delineated margins in this study, although no significant difference was found between the histologic phenotypes.…”

Section: Discussionmentioning

confidence: 97%

“…25 The authors also found that tumor invasion into the ventricles was inhibited via a nonmechanical force in the ependymal region. 25 Notably, significant differences were observed in the survival prognosis of patients with DHGs-G34m showing ill-defined margins and those with DHGs-G34m showing well-delineated margins in this study, although no significant difference was found between the histologic phenotypes. Importantly, invasion of gliomas can also occur in normalappearing surrounding parenchyma on conventional MRI.…”

Section: Discussionmentioning

confidence: 97%

“…However, further studies are required to determine whether this temporal interval is unique to DHGs‐G34m. A recent study identified ependymal contact in the majority of glioblastomas (237/357, 66%), and observed ventricular invasion of the tumors in only 34/237 patients (14.3%) 25 . The authors also found that tumor invasion into the ventricles was inhibited via a nonmechanical force in the ependymal region 25 …”

Section: Discussionmentioning

confidence: 99%

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Neuroimaging features of diffuse hemispheric glioma, H3 G34‐mutant: A case series and systematic review

Kurokawa

Baba

Kurokawa

et al. 2021

Journal of Neuroimaging

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Background and Purpose: Diffuse hemispheric gliomas, H3 G34-mutant (DHGs-G34m), are newly recognized malignant brain tumors characterized by histone gene mutations.However, the neuroradiologic characteristics of these tumors require elucidation. We reviewed the demographic, clinical, and neuroradiological features of DHGs-G34m.Methods: Data were extracted using a database search in MEDLINE, SCOPUS, and Google Scholar in June 2021. Studies assessing pathologically proven DHGs-G34m with each patient's information and neuroradiological findings were included. After screening and reviewing 332 abstracts, 12 articles including 56 cases met the criteria. We also added the findings for three patients evaluated in our hospital. Two board-certified radiologists reviewed all demographic, clinical, and neuroradiological findings of each study. One board-certified pathologist reviewed all pathological data of each study. Kaplan-Meier analyses with log-rank tests were performed to compare the survival between patients with different tumor margin characteristics (well-delineated and ill-defined). Results:The median patient age at diagnosis was 19 years (range, 6-66 years), and 31/59 patients (52.5%) were men. Supratentorial tumors were observed in all patients (59/59, 100%). Frequent contact with leptomeninges (92.3%) and ependymal regions (87.5%) was observed. The 1-and 2-year survival rates after initial surgery were 66.7% and 40.0%, respectively. DHGs-G34m with ill-defined and well-delineated margins showed significant differences in survival (p = .04).Conclusions: DHGs-G34m occur most often in the supratentorial regions of adolescents.Prognosis varies among patients. Evaluation of tumor margins may provide prognostic value.

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“…However, the lack of a definite margin in gliomas results in the difficult application of the en-bloc technique [ 30 ]. However, as we previously described [ 14 , 31 ], membranous structures, including the pia mater and ependyma, could be used as surgical margins because of their blocking effect on tumor cells. In addition, we consider that the en-bloc technique has several other advantages to glioma surgery.…”

Section: Discussionmentioning

confidence: 99%

Applying the en-bloc technique in corpus callosum glioblastoma surgery contributes to maximal resection and better prognosis: a retrospective study

Que,

Yuan,

Tan

et al. 2024

BMC Surg

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Background Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. Methods A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. Results Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P < 0.001; r = 0.720, P < 0.001 for PSM analysis), indicating that applying the en-bloc technique could contribute to enlarged maximal resection. Further survival analysis confirmed that applying the en-bloc technique and achieving supramaximal resection could significantly prolong OS and PFS, and multivariate analysis suggested that tumor location, pathology, EOR and the en-bloc technique could be regarded as independent prognostic indicators for OS in patients with ccGBMs, and pathology, EOR and the en-bloc technique were independently correlated with patient’s PFS. Interestingly, the en-bloc technique also provided a marked reduction in the risk of tumor recurrence compared with the no-en-bloc technique in tumors undergoing TR, indicating that the essential role of the en-bloc technique in ccGBM surgery (HR: 0.712; 95% CI: 0.535–0.947; P = 0.02). Conclusions The en-bloc technique could contribute to achieving an enlarged maximal resection and could significantly prolong overall survival and progression-free survival in patients with ccGBMs.

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

Cited by 5 publications

References 34 publications

Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone

Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone

Neuroimaging features of diffuse hemispheric glioma, H3 G34‐mutant: A case series and systematic review

Applying the en-bloc technique in corpus callosum glioblastoma surgery contributes to maximal resection and better prognosis: a retrospective study

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