Dataset Information

Galvanotactic Migration of Glioblastoma and Brain Metastases Cells.

ABSTRACT: Galvanotaxis, the migration along direct current electrical fields, may contribute to the invasion of brain cancer cells in the tumor-surrounding tissue. We hypothesized that pharmacological perturbation of the epidermal growth factor (EGF) receptor and downstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevent galvanotactic migration. In our study, patient-derived glioblastoma and brain metastases cells were exposed to direct current electrical field conditions. Velocity and direction of migration were estimated. To determine the effects of EGF receptor antagonist afatinib and AKT inhibitor capivasertib, assays of cell proliferation, apoptosis and immunoblot analyses were performed. Both inhibitors attenuated cell proliferation in a dose-dependent manner and induced apoptosis. We found that most of the glioblastoma cells migrated preferentially in an anodal direction, while brain metastases cells were unaffected by direct current stimulations. Afatinib presented only a mild attenuation of galvanotaxis. In contrast, capivasertib abolished the migration of glioblastoma cells without genetic alterations in the PI3K/AKT pathway, but not in cells harboring PTEN mutation. In these cells, an increase in the activation of ERK1/2 may in part substitute the inhibition of the AKT pathway. Overall, our data demonstrate that glioblastoma cells migrate in the electrical field and the PI3K/AKT pathway was found to be highly involved in galvanotaxis.

SUBMITTER: Lange F

PROVIDER: S-EPMC9027426 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Galvanotactic Migration of Glioblastoma and Brain Metastases Cells.

Lange Falko F Venus Jakob J Shams Esfand Abady Daria D Porath Katrin K Einsle Anne A Sellmann Tina T Neubert Valentin V Reichart Gesine G Linnebacher Michael M Köhling Rüdiger R Kirschstein Timo T

Life (Basel, Switzerland) 20220414 4

Galvanotaxis, the migration along direct current electrical fields, may contribute to the invasion of brain cancer cells in the tumor-surrounding tissue. We hypothesized that pharmacological perturbation of the epidermal growth factor (EGF) receptor and downstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevent galvanotactic migration. In our study, patient-derived glioblastoma and brain metastases cells were exposed to direct current electrical field conditions. Velocity and direction ...[more]

PMID: 35455071

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Project description:ObjectivesTo identify qualitative VASARI (Visually AcceSIble Rembrandt Images) Magnetic Resonance (MR) Imaging features for differentiation of glioblastoma (GBM) and brain metastasis (BM) of different primary tumors.Materials and methodsT1-weighted pre- and post-contrast, T2-weighted, and T2-weighted, fluid attenuated inversion recovery (FLAIR) MR images of a total of 239 lesions from 109 patients with either GBM or BM (breast cancer, non-small cell (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small-cell lung cancer (SCLC)) were included. A set of adapted, qualitative VASARI MR features describing tumor appearance and location was scored (binary; 1 = presence of feature, 0 = absence of feature). Exploratory data analysis was performed on binary scores using a combination of descriptive statistics (proportions with 95% binomial confidence intervals), unsupervised methods and supervised methods including multivariate feature ranking using either repeated fitting or recursive feature elimination with Support Vector Machines (SVMs).ResultsGBMs were found to involve all lobes of the cerebrum with a fronto-occipital gradient, often affected the corpus callosum (32.4%, 95% CI 19.1-49.2), and showed a strong preference for the right hemisphere (79.4%, 95% CI 63.2-89.7). BMs occurred most frequently in the frontal lobe (35.1%, 95% CI 28.9-41.9) and cerebellum (28.3%, 95% CI 22.6-34.8). The appearance of GBMs was characterized by preference for well-defined non-enhancing tumor margin (100%, 89.8-100), ependymal extension (52.9%, 36.7-68.5) and substantially less enhancing foci than BMs (44.1%, 28.9-60.6 vs. 75.1%, 68.8-80.5). Unsupervised and supervised analyses showed that GBMs are distinctively different from BMs and that this difference is driven by definition of non-enhancing tumor margin, ependymal extension and features describing laterality. Differentiation of histological subtypes of BMs was driven by the presence of well-defined enhancing and non-enhancing tumor margins and localization in the vision center. SVM models with optimal hyperparameters led to weighted F1-score of 0.865 for differentiation of GBMs from BMs and weighted F1-score of 0.326 for differentiation of BM subtypes.ConclusionVASARI MR imaging features related to definition of non-enhancing margin, ependymal extension, and tumor localization may serve as potential imaging biomarkers to differentiate GBMs from BMs.

Dataset Information

Galvanotactic Migration of Glioblastoma and Brain Metastases Cells.

Publications

Galvanotactic Migration of Glioblastoma and Brain Metastases Cells.

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