Reversible electroporation enhances invasive properties of patient-derived glioblastoma cells

Abstract

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 electroporation using transwell assay and RNA transcriptome analysis, respectively.

Results. Reversible electroporation at 1.0 kV/cm enhanced invasion in both cell lines. Specifically, the number of invading cells increased by a median of 3.74-fold (274 %) in the NIB140 CORE and by 1.30-fold (30 %) in the NIB216 cell lines. Transcriptomic profiling in NIB140 CORE cell line identified modulation of genes linked to extracellular matrix organization, ion channel activity, and cytoskeletal remodelling, supporting the activation of invasion-related pathways.

Conclusions. These findings highlight a potential risk of pro-invasive responses in GB cells surviving within the peripheral zone of electroporation-treated area. The two tested cell lines showed distinct transcriptomic and functional responses, underscoring patient intertumoral heterogeneity. However, given the limitations of 2D cultures, future studies should confirm these effects in more physiologically relevant 3D models such as multicellular spheroids or patient-derived organoids.