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Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitro Cover

Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitro

Open Access
|Dec 2025

References

  1. Kotnik T, Rems L, Tarek M, Miklavčič D. Membrane electroporation and electropermeabilization: mechanisms and models. Annu Rev Biophys 2019; 48: 63-91. doi: 10.1146/annurev-biophys-052118-115451
  2. Aycock KN, Davalos RV. Irreversible electroporation: background, theory, and review of recent developments in clinical oncology. Bioelectr 2019; 1: 214-234. doi: 10.1089/bioe.2019.0029
  3. Jacobs EJ, Rubinsky B, Davalos RV. Pulsed field ablation in medicine: irreversible electroporation and electropermeabilization theory and applications. Radiol Oncol 2025; 59(4): 535-550.; 59: 1-22. doi: 10.2478/raon-2025-0011
  4. Mir LM, Gehl J, Serša G, Collins CG, Garbay JR, Billard V, et al. Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes. EJC Suppl 2006; 4: 14-25. doi: 10.1016/j.ejc-sup.2006.08.003
  5. Miklavčič D, Mali B, Kos B, Heller R, Serša G. Electrochemotherapy: from the drawing board into medical practice. BioMed Eng Online 2014; 13: 29. doi: 10.1186/1475-925X-13-29
  6. Grochans S, Cybulska AM, Siminska D, Korbecki J, Kojder K, Chlubek D, et al. Epidemiology of glioblastoma multiforme-literature review. Cancers 2022; 14: 2412. doi: 10.3390/cancers14102412
  7. Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol 2022; 24(Suppl 5): v1-95. doi: 10.1093/neuonc/noac202
  8. Obrador E, Moreno-Murciano P, Oriol-Caballo M, Lopez-Blanch R, Pineda B, Gutierrez-Arroyo JL, et al. Glioblastoma therapy: past, present and future. Int J Mol Sci 2024; 25: 2529. doi: 10.3390/ijms25052529
  9. Liu Y, Zhou F, Ali H, Lathia JD, Chen P. Immunotherapy for glioblastoma: current state, challenges, and future perspectives. Cell Mol Immunol 2024; 21: 1354-75. doi: 10.1038/s41423-024-01226-x
  10. Pichol-Thievend C, Anezo O, Pettiwala AM, Bourmeau G, Montagne R, Lyne AM, et al. VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance. Nat Commun 2024; 15: 3602. doi: 10.1038/s41467-024-47985-z
  11. Garcia P, Rossmeisl JH, Neal R, Ellis TL, Olson JD, Henao-Guerrero N, et al. Intracranial nonthermal irreversible electroporation: in vivo analysis. J Membr Biol 2010; 236: 127-36. doi: 10.1007/s00232-010-9284-z
  12. Ellis TL, Garcia PA, Rossmeisl JH, Henao-Guerrero N, Robertson J, Davalos RV. Nonthermal irreversible electroporation for intracranial surgical applications. J Neurosurg 2011; 114: 681-8. doi: 10.3171/2010.5.JNS091448
  13. Rossmeisl JH, Garcia PA, Roberston JL, Ellis TL, Davalos RV. Pathology of nonthermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain. J Vet Sci 2013; 14: 433-40. doi: 10.4142/jvs.2013.14.4.433
  14. Rossmeisl JH, Garcia PA, Pancotto TE, et al. Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas. J Neurosurg 2015; 123: 1008-25. doi: 10.3171/2014.12.JNS141768
  15. Garcia PA, Kos B, Rossmeisl JH, Pavliha D, Miklavčič D, Davalos RV. Predictive therapeutic planning for irreversible electroporation treatment of spontaneous malignant glioma. Med Phys 2017; 44: 4968-80. doi: 10.1002/mp.12401
  16. Arena CB, Sano MB, Rossmeisl JH, Caldwell JL, Garcia PA, Rylander MN, et al. High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction. Biomed Eng Online 2011; 10: 102. doi: 10.1186/1475-925X-10-102
  17. Latouche EL, Arena CB, Ivey JW, Garcia PA, Pancotto TE, Pavlisko N, et al. High-frequency irreversible electroporation for intracranial meningioma: a feasibility study in a spontaneous canine tumor model. Technol Cancer Res Treat 2018; 17: 1533033818785285. doi: 10.1177/1533033818785285
  18. Salford LG, Persson BR, Brun A, Ceberg CP, Kongstad PC, Mir LM. A new brain tumour therapy combining bleomycin with in vivo electropermeabilization. Biochem Biophys Res Commun 1993; 194: 938-43. doi: 10.1006/bbrc.1993.1911
  19. Agerholm-Larsen B, Iversen HK, Ibsen P, Moller JM, Mahmood F, Jensen KS, et al. Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. Cancer Res 2011; 71: 3753-62. doi: 10.1158/0008-5472.CAN-11-0451
  20. Sharabi S, Guez D, Daniels D, Cooper I, Atrakchi D, Liraz-Zaltsman S, et al. The application of point source electroporation and chemotherapy for the treatment of glioma: a randomized controlled rat study. Sci Rep 2020; 10: 2178. doi: 10.1038/s41598-020-59152-7
  21. Linnert M, Iversen HK, Gehl J. Multiple brain metastases – current management and perspectives for treatment with electrochemotherapy. Radiol Oncol 2012; 46: 271-8. doi: 10.2478/v10019-012-0042-y
  22. Jacobs Iv EJ, Campelo SN, Charlton A, Altreuter S, Davalos RV. Characterizing reversible, irreversible, and calcium electroporation to generate a burstdependent dynamic conductivity curve. Bioelectrochemistry 2024; 155: 108580. doi: 10.1016/j.bioelechem.2023.108580
  23. Nakagawa H, Farshchi-Heydari S, Maffre J, Sharma T, Govari A, Beeckler C, et al. Evaluation of ablation parameters to predict irreversible lesion size during pulsed field ablation. Circ Arrhythm Electrophysiol 2024; 17: e012814. doi: 10.1161/CIRCEP.124.012814
  24. Miklavčič D, Šemrov D, Mekid H, Mir LM. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy. Biochim Biophys Acta Gen Subj 2000; 1523: 73-83. doi: 10.1016/S0304-4165(00)00101-X
  25. Amin SB, Anderson KJ, Boudreau CE, Martinez-Ledesma E, Kocakavuk E, Johnson KC, et al. Comparative molecular life history of spontaneous canine and human gliomas. Cancer Cell 2020; 37: 243-57.e7. doi: 10.1016/j. ccell.2020.01.004
  26. Sahu U, Barth RF, Otani Y, McCormack R, Kaur B. Rat and mouse brain tumor models for experimental neuro-oncology research. J Neuropathol Exp Neurol 2022; 81: 312-29. doi: 10.1093/jnen/nlac021
  27. Chow L, Wheat W, Ramirez D, Impastato R, Dow S. Direct comparison of canine and human immune responses using transcriptomic and functional analyses. Sci Rep 2024; 14: 2207. doi: 10.1038/s41598-023-50340-9
  28. Xie Y, Bergström T, Jiang Y, Johnson P, Marinescu VD, Lindberg N, et al. The human glioblastoma cell culture resource: validated cell models representing all molecular subtypes. EBioMedicine 2015; 2: 1351-1363 doi: 10.1016/j. ebiom.2015.08.026
  29. Steinle M, Palme D, Misovic M, Rudner J, Dittmann K, Lukowski R, et al. Ionizing radiation induces migration of glioblastoma cells by activating BK K(+) channels. Radiother Oncol 2011; 101: 122-126. doi: 10.1016/j. radonc.2011.05.069
  30. Blažič A, Guinard M, Leskovar T, O’Connor RP, Rems L. Long-term changes in transmembrane voltage after electroporation are governed by the interplay between nonselective leak current and ion channel activation. Bioelectrochemistry 2025; 161: 108802. doi: 10.1016/j.bioelechem.2024.108802
  31. Younes S, Mourad N, Salla M, Rahal M, Hammoudi Halat D. Potassium ion channels in glioma: from basic knowledge into therapeutic applications. Membranes 2023; 13: 434. doi: 10.3390/membranes13040434
  32. D’Alessandro G, Monaco L, Catacuzzeno L, Antonangeli F, Santoro A, Esposito V, et al. Radiation increases functional KCa3.1 expression and invasiveness in glioblastoma. Cancers 2019; 11: 279. doi: 10.3390/cancers11030279
  33. Novak M, Majc B, Malavolta M, Porčnik A, Mlakar J, Hren M, et al. The Slovenian translational platform GlioBank for brain tumor research: identification of molecular signatures of glioblastoma progression. Neurooncol Adv 2025; 7: vdaf015. doi: 10.1093/noajnl/vdaf015
  34. Murphy KR, Aycock KN, Hay AN, Rossmeisl JH, Davalos RV, Dervisis NG. High-frequency irreversible electroporation brain tumor ablation: exploring the dynamics of cell death and recovery. Bioelectrochemistry 2022; 144: 108001. doi: 10.1016/j.bioelechem.2021.108001
  35. Partridge BR, Kani Y, Lorenzo MF, Campelo SN, Allen IC, Hinckley J, et al. High-frequency irreversible electroporation (H-FIRE) induced blood-brain barrier disruption is mediated by cytoskeletal remodeling and changes in tight junction protein regulation. Biomedicines 2022; 10: 1384. doi: 10.3390/biomedicines10061384
  36. Batista Napotnik T, Miklavčič D. In vitro electroporation detection methods – An overview. Bioelectrochemistry 2018; 120: 166-182. doi: 10.1016/j. bioelechem.2017.12.005
  37. Blažič A, Šmerc R, Polajžer T, Miklavčič D, Rems L. Reassessing lidocaine as an electroporation sensitizer in vitro. Sci Rep 2025; 15: 25593. doi: 10.1038/s41598-025-11695-3
  38. Hira VV, Breznik B, Van Noorden CJ, Lah T, Molenaar RJ. 2D and 3D in vitro assays to quantify the invasive behavior of glioblastoma stem cells in response to SDF-1α. Biotechniques 2020; 69: 339-46. doi: 10.2144/btn-2020-0046
  39. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9: 676-82. doi: 10.1038/nmeth.2019
  40. Morozas A, Malyško-Ptašinskė V, Kulbacka J, Ivaška J, Ivaškienė T, Novickij V. Electrochemotherapy for head and neck cancers: possibilities and limitations. Front Oncol 2024; 14: 1353800. doi: 10.3389/fonc.2024.1353800
  41. Li A, Walling J, Kotliarov Y, Center A, Steed MA, Ahn SJ, et al. Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res 2008; 6: 21-30. doi: 10.1158/1541-7786.MCR-07-0280
  42. Keller S, Schmidt MHH. EGFR and EGFRvIII promote angiogenesis and cell invasion in glioblastoma: combination therapies for an effective treatment. Int J Mol Sci 2017; 18: 1295. doi: 10.3390/ijms18061295
  43. Abed T, Ganser K, Eckert F, Stransky N, Huber SM. Ion channels as molecular targets of glioblastoma electrotherapy. Front Cell Neurosci 2023; 17: 1133984. doi: 10.3389/fncel.2023.1133984
  44. Wei R, Zhou J, Bui B, Liu X. Glioma actively orchestrate a self-advantageous extracellular matrix to promote recurrence and progression. BMC Cancer 2024; 24: 974. doi: 10.1186/s12885-024-12751-3
  45. Aitchison EE, Dimesa AM, Shoari A. Matrix metalloproteinases in glioma: drivers of invasion and therapeutic targets. BioTech 2025; 14: 28. doi: 10.3390/biotech14020028
  46. Lehmann S, Boekhorst VT, Odenthal J, Bianchi R, Helvert S, Ikenberg K, et al. Hypoxia induces a HIF-1-dependent transition from collective-to-amoeboid dissemination in epithelial cancer cells. Curr Biol 2017; 27: 392-400. doi: 10.1016/j.cub.2016.11.057
  47. Graybill PM, Davalos RV. Cytoskeletal disruption after electroporation and its significance to pulsed electric field therapies. Cancers 2020; 12: 1132. doi: 10.3390/cancers12051132
  48. Azuaje F, Tiemann K, Niclou SP. Therapeutic control and resistance of the EGFR-driven signaling network in glioblastoma. Cell Commun Signal 2015; 13: 23. doi: 10.1186/s12964-015-0098-6
  49. Wang X, Hong T, Liu G, Rao J, Shi F, Wang H, et al. High-frequency irreversible electroporation suppresses invasion and metastasis by targeting SIRT1/2 in highly invasive tumor cells: an in vitro study. Bioelectrochemistry 2025; 166: 109036. doi: 10.1016/j.bioelechem.2025.109036
  50. Casciati A, Tanori M, Gianlorenzi I, Rampazzo E, Persano L, Viola G, et al. Effects of ultra-short pulsed electric field exposure on glioblastoma cells. Int J Mol Sci 2022; 23: 3001. doi: 10.3390/ijms23063001
  51. Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: good news and bad news. Sci Transl Med 2016; 8: 354re3. doi: 10.1126/scitranslmed.aaf6853
  52. Cheng L, Wu Q, Guryanova OA, Huang Q, Rich JN, Bao S, et al. Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun 2011; 406: 643-8. doi: 10.1016/j.bbrc.2011.02.123
  53. Prager BC, Bhargava S, Mahadev V, Hubert CG, Rich JN. Glioblastoma stem cells: driving resilience through chaos. Trends Cancer 2020; 6: 223-235. doi: 10.1016/j.trecan.2020.01.009
  54. Garcia PA, Pancotto T, Rossmeisl JH, Henao-Guerrero N, Gustafson NR, Daniel GB, et al. Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol Cancer Res Treat 2011; 10: 73-83. doi: 10.7785/tcrt.2012.500181
  55. Dasari S, Bernard Tchounwou P. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-378. doi: 10.1016/j. ejphar.2014.07.025
  56. Serša G, Čemažar M, Miklavčič D, Rudolf Z. Electrochemotherapy of tumours. Radiol Oncol 2006; 40: 163-74. [internet]. [cited 2025 Jul 15]. Available at https://www.radioloncol.com/index.php/ro/article/view/1258
  57. Lorenzo MF, Thomas SC, Kani Y, Hinckley J, Lee M, Adler J, et al. Temporal characterization of blood–brain barrier disruption with high-frequency electroporation. Cancers 2019; 11: 1850. doi: 10.3390/cancers11121850
  58. Sharabi S, Bresler Y, Ravid O, Shemesh C, Atrakchi D, Schnaider-Beeri M, et al. Transient blood-brain barrier disruption is induced by low pulsed electrical fields in vitro: an analysis of permeability and trans-endothelial electric resistivity. Drug Deliv 2019; 26: 459-69. doi: 10.1080/10717544.2019.1571123
  59. Todorovic V, Sersa G, Mlakar V, Glavac D, Flisar K, Cemazar M. Metastatic potential of melanoma cells is not affected by electrochemotherapy. Melanoma Res 2011; 21: 196-205. doi: 10.1097/CMR.0b013e328337abd7
  60. Todorovic V, Sersa G, Mlakar V, Glavac D, Cemazar M. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin. Radiol Oncol 2012; 46: 32-45. doi: 10.2478/v10019-012-0010-6
  61. Auffinger B, Tobias AL, Han Y, Lee G, Guo D, Dey M, et al. Conversion of differentiated cancer cells into cancer stem-like cells in a glioblastoma model after primary chemotherapy. Cell Death Differ 2014; 21: 1119-1131. doi: 10.1038/cdd.2014.31
  62. Wang Z, Zhang H, Xu S, Liu Z, Cheng Q. The adaptive transition of glioblastoma stem cells and its implications on treatments. Sig Transduct Target Ther 2021; 6: 1-13. doi: 10.1038/s41392-021-00491-w
  63. Arroyo JP, Jacobs EJ, Ahmad RN, Amin AJ, Verbridge SS, Davalos RV. Characterization of glioma spheroid viability and metastatic potential following monophasic and biphasic pulsed electric fields. Bioelectrochemistry 2025; 165: 109005. doi: 10.1016/j.bioelechem.2025.109005
DOI: https://doi.org/10.2478/raon-2025-0058 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
Language: English
Page range: 535 - 550
Submitted on: Aug 11, 2025
Accepted on: Sep 29, 2025
Published on: Dec 16, 2025
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2025 Anja Blazic, Bernarda Majc, Metka Novak, Barbara Breznik, Lea Rems, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.