Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitro
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PROVIDER: PRJNA1303707 | ENA |
REPOSITORIES: ENA
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Project description:Background. Electroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells. Materials and methods. Five patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electro-poration using transwell assay and RNA transcriptome analysis, respectively. Results. Reversible electroporation at 1.0 kV/cm enhanced invasion in a cell line-dependent manner. NIB140 CORE showed a consistent and pronounced increase, with a median of 3.74-fold (274 %) higher number of invading cells compared to sham control. In contrast, NIB216 CORE exhibited only a modest increase in invasion (1.30-fold; 30 %). Transcriptomic profiling identified modulation of genes linked to extracellular matrix or-ganization and ion channel activity in NIB140 CORE, and cytoskeletal remodelling in NIB216 CORE, indicating the activation of invasion-related pathways. Conclusions. These findings highlight a potential risk of pro-invasive responses in GB cells. In tumour ablation with irreversible electroporation, this concern relates to cells in the pe-ripheral zone that may experience only sublethal electric fields, while in electrochemo-therapy, a similar risk may arise if permeabilized cells are not effectively eliminated due to insufficient local drug delivery. Nevertheless, the two tested cell lines responded differ-ently, underscoring patient-specific heterogeneity and the need for validation in more physiologically relevant models.
2025-08-31 | GSE305017 | GEO
Project description:In this project we aimed at deciphering modulation in genes expression induced by external pulsed electric fields applied in reversible electroporation-based treatments. Thanks to their local application and transient effects, physical stimuli appear as attractive tools to remodel extracellular matrix, which was the point of interest in our to be published study. We assessed the potential of pulsed electric field technology, classically applied to drug delivery, to induce collagen remodeling at the tissue scale. A sophisticated in vitro tissue-engineered human dermal substitute, a tissue model rich in endogeneous extracellular matrix such as collagens, was used to demonstrate the effects of microsecond and millisecond pulsed electric fields applied respectively in electrochemotherapy (ECT) treatment and gene electrotransfer (GET) strategy. Our analyses, focused on matrisome genes and extracellular matrix remodeling, underpin that pulsed electric fields, a technology already approved for clinical use combined with anti-cancer agents, are particularly promising to provide local and effective treatment of abnormal extracellular matrix. Part of this dataset was used to describe how pulsed electric field on its own (with no addition of external drugs) induce extracellular matrix (ECM) remodeling at human dermal scale, by focusing at genes related to matrisome subset. In this manuscript to be published, electrochemotherapy (ECT) parameters were named SP for "short pulses" and gene electrotransfer (GET) parameters were named LP for "long pulses". W demonstrated that these both types of electric parameters inducing reversible electroporation of the cells whitin the dermal tissue substitute induced 1) a rapid modulation (4h after electrostimulation) of mRNA’s genes composing the matrisome, particularly a down-regulation of pro-collagens and ECM maturation’s enzymes such as transglutaminase TG2 and LOX-like; 2) a transient decrease in pro-collagens production and hydroxyproline tissue content within a week after electrostimulation; 3) a long-lasting ROS-dependent over-activation of MMPs for at least 48h and 4) a down-regulation at both mRNA and protein level of pro-fibrotic TGF-β.
2021-07-26 | GSE180644 | GEO
Project description:Gene expression modulation in human dermal substitute exposed to reversible electroporation (ECT or GET types)
| PRJNA749020 | ENA
Project description:The persistence of Glioblastoma Stem-like Cells (GSCs) may account for the high lethality of glioblastoma patients. The GSC reservoir typically resides close to blood vessels, where these cells receive maintenance signals. Upon unfavorable conditions, GSCs escape these niches and spread by exploiting the pre-existing brain vasculature. In both scenarios, GSCs interact with the vascular interface, including the endothelial cells and their matrix. How cell adhesion encountered in their microenvironment serves GSC fate remains ill-defined. By combining ex vivo models, including decellularized matrices, cell co-culture, and organotypic slices, we identified that Junctional Adhesion Molecule C (JAMC) tethers GSCs to endothelial surface. Functionally, JAMC-/- GSCs exhibit an extended spreading on various endothelial-borne supports, with exacerbated invasive, migratory, and mesenchymal-like behaviors, that eventually eroded the survival of GSC tumor-bearing mice. Label-free quantitative proteomics next unveiled that JAMC deletion elicits an up-regulation of integrin expression, concurrent to a down-regulation of the integrin negative regulator, SHARPIN. Data mining of spatial transcriptomics confirmed the association between glioblastoma invasion and the expression pattern of JAMC. While JAMC may provide a retention signal in endothelial niches, the landscape of adhesion molecules anchoring GSCs to vascular surfaces may ultimately coordinate cell migration in defined glioblastoma territories.
2025-08-28 | PXD062679 | Pride
Project description:The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts therapeutic access and surgical resection. Therefore, effective anti-invasive strategies of GBM cells can be key to increase the efficacy of chemotherapy against this devastating disease. As cancer stem or initiating cells are considered to retain the tumorigenic potential in a number of tumors including glioblastoma, we studied the invasion capabilities of glioblastoma initiating cells (GICs) that were isolated from the peritumoral (PT) tissue, which surrounds the tumor mass (TM) and remains in the brain after tumor removal. We found that PT-GICs are less proliferative but more invasive compared to TM-GICs. Gene expression arrays of cells derived from the tumor mass and the peritumoral tissue of three glioblastoma cases
2015-05-13 | E-GEOD-37985 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is a highly heterogeneous malignant brain tumour. We took multi-region spatially separated samples from tumours and isolated invasive GBM cells using FACS based on 5ALA of near normal brain parenchyma. RNAseq was then performed to compare expression profiles for tumour cells from different microenvironment.
2020-12-15 | E-MTAB-8743 | biostudies-arrayexpress
Project description:The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts therapeutic access and surgical resection. Therefore, effective anti-invasive strategies of GBM cells can be key to increase the efficacy of chemotherapy against this devastating disease. As cancer stem or initiating cells are considered to retain the tumorigenic potential in a number of tumors including glioblastoma, we studied the invasion capabilities of glioblastoma initiating cells (GICs) that were isolated from the peritumoral (PT) tissue, which surrounds the tumor mass (TM) and remains in the brain after tumor removal. We found that PT-GICs are less proliferative but more invasive compared to TM-GICs.
2015-05-13 | GSE37985 | GEO
Project description:Localized Electroporation (LEP) has emerged as an effective tool for intracellular delivery and non-destructive analysis of cells. However, little is known about the effects of LEP on cellular gene expression which may adversely impact their downstream phenotype. Here we use single cell RNA sequencing to dissect the effects of LEP on murine neural stem cell (NSC) gene expression and compare it to Bulk Electroporation (BEP).
2023-03-10 | GSE205507 | GEO
Project description:Background: Safe and sensitive methods for glioblastoma diagnosis and disease monitoring are urgently needed. Exosomes are nano-sized extracellular vesicles that contain molecules characteristic of their cell-of-origin, including microRNA. Exosomes released by glioblastoma tumors cross the blood-brain-barrier ino the peripheral circulation. Methods: Serum exosomal-microRNA isolated from IDH-wildtype glioblastoma (n=12) and IDH-mutant glioma grades II-III (n=10) were analyzed using small-RNA next generation sequencing and compared to age- and gender-matched healthy controls. Differentially expressed miRNAs (|fold change|³2 and p-value ≤ 0.05 in three statistical tests, Fischer-exact, t-test, and Wilcoxon) were identified and the predictive power of individual and subsets of miRNAs were tested using univariate (logistic regression) and multivariate (Random Forest) analyses. Additional glioblastoma sera (n=4) and independent sets of healthy (n=9) and non-glioma (n=10) controls were used to further test the predictive power of our glioblastoma miRNA signature. Results: Twenty-six miRNAs were differentially expressed in glioblastoma relative to healthy controls. Seven miRNAs (miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p and miR-543) were the most stable for classifying glioblastoma, achieving a predictive power of 91.7%. Strikingly, the combined expressions of miR-182-5p, miR-328-3p miR-485-3p miR-486-5p distinguished glioblastoma patients from controls with perfect accuracy. This miRNA panel was able to correctly classify all specimens in validation cohorts (n=23). An analogous approach was used to identify 23 dysregulated miRNAs in IDH-mutant gliomas, including a distinct subset of stable miRNAs for classifying patients with lower-grade IDH-mutant gliomas. Conclusions: Our serum exosomal-miRNA signature can accurately diagnose glioblastoma preoperatively. These findings have significant scope to revolutionize glioblastoma tumor diagnosis and disease monitoring. IMPORTANCE OF STUDY: There is a real need for accurate biomarkers that can measure glioblastoma disease activity and treatment response in a safe and timely manner. This study demonstrates that exosome-associated microRNAs have exceptional utility as blood-based biomarkers in glioma patients. This work also shows the potential for exosomal microRNA profiles to be used for glioma subtyping, grading and determining mutational states. The development of specific, sensitive and non-invasive screening tests would have significant clinical benefit by reducing costs of treatment monitoring, improving accessibility and quality-of-life measures. Moreover, such tests have the potential to provide objectively measured surrogate endpoints to allow clinical trial protocols to be more dynamic and adaptive.
2018-11-14 | GSE122488 | GEO
Project description:Glioblastomas are brain tumors that are derived from astrocytes or oligodendrocytes. These tumors have a heterogeneous structure composed of a necrotic and vascularized center and an invasive periphery. The rapid development of glioblastoma and its ability to invade surrounding tissues makes it a complex pathology to treat, and the average survival of patients ranging from 12 to 15 months. The first and second lines of treatment, based on the Stupp protocol, consisting of the resection of the tumor mass and adjuvant temozolomide treatment and/or radiotherapy, only allow delaying recurrence for a few months. The additional use of anti-angiogenic treatment, despite its initial effects on tumor vascularization and the central tumor core, invariably leads to tumor escape. Tumor cell invasion is the central element in tumor recurrence. It is therefore important to understand the mechanisms of tumor invasion and understand the interactions between tumor cells and their microenvironment. Here, we performed proteomics analysis of glioblastoma core and invasive areas, tumor derived from a patient xenograft. Bioinformatics data analysis allowed us to identify molecules that may represent markers of tumor invasion. We established novel protein signatures such as phopholipoprotein-1 (PLP1), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) or Dynamin-1 (DNM1), and validated them in tumor samples. Finally, a functional validation was carried out in in vitro experiments. To conclude, our results report novel unexpected proteins that are involved in GBM invasion and that may constitute novel therapeutic targets.
2021-06-10 | PXD012791 | Pride