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The endothelial cytoskeleton as a target of electroporation-based therapies
Abstract
Electroporation-based therapies, such as electrochemotherapy and electrogene therapy, result in the disruption of blood vessel networks in vivo and cause changes in blood flow and vascular permeability. The effects of electroporation on the cytoskeleton of cultured primary endothelial cells and on endothelial monolayer permeability were investigated to elucidate possible mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were electroporated in situ and then immunofluorescence staining for filamentous actin, beta-tubulin, vimentin, and VE-cadherin as well as Western blotting analysis of levels of phosphorylated myosin light chain and cytoskeletal proteins were performed. Endothelial permeability was determined by monitoring the passage of FITC-coupled dextran through endothelial monolayers. Exposure of endothelial cells to electric pulses resulted in a profound disruption of microfilament and microtubule cytoskeletal networks, loss of contractility, and loss of vascular endothelial cadherin from cell-to-cell junctions immediately after electroporation. These effects were voltage dependent and reversible because cytoskeletal structures recovered within 60 min of electroporation with up to 40 V, without any significant loss of cell viability. The cytoskeletal effects of electroporation were paralleled by a rapid increase in endothelial monolayer permeability. These results suggest that the remodeling of the endothelial cytoskeleton and changes in endothelial barrier function could contribute to the vascular disrupting actions of electroporation-based therapies and provide an insight into putative mechanisms responsible for the observed increase in permeability and cessation of blood flow in vivo.
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“To better understand the effects that electroporation can have on the cell cytoskeleton, Kanthou and colleagues studied endothelial cells with fluorescence imaging and found that at electric field strengths in the 50–200 V/cm range, electroporation of endothelial cells is not only possible, but imaging also revealed significant, reversible disruption of interphase microtubules and actin filaments”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [66]
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Metadata
- Authors
- Kanthou, C., Kranjc, S., Sersa, G., Tozer, G., Zupanic, A., & Cemazar, M.
- Affiliations
- Royal Hallamshire Hospital (GB)
- Institute of Oncology Ljubljana (SI)
- 2Department of Experimental Oncology, Institute of Oncology Ljubljana; and
- 3Faculty of Electrical Engineering, Laboratory of Biocybernetics, University of Ljubljana, Ljubljana, Slovenia
- Venue
- Molecular Cancer Therapeutics
- Published
- 2006-12-01
- Volume
- 5
- Issue
- 12
- Pages
- 3145-3152
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- OpenAlex
- W2163517119
- Cited by
- 129
- References
- 41
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 13 · 2015: 5 · 2014: 8 · 2013: 11 · 2012: 8
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Cancer Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Keywords
- electroporation, endothelial cytoskeleton, electrochemotherapy, vascular disrupting agents, endothelial permeability, endothelial barrier function, VE-cadherin, F-actin, microtubules, myosin light chain phosphorylation, human umbilical vein endothelial cells, vascular permeability
- MeSH terms
- Cadherin 5, Actins, Cytoskeleton, Humans, Intermediate Filaments, Actin Cytoskeleton, Microtubules, Myosins, Neoplasms, Antigens, CD, Cadherins, Electroporation, Endothelial Cells
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