GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells
Despite their genetic diversity, metastatic cells converge on similar physical constraints during tumor progression. At the nanoscale, these forces can induce substantial molecular deformations, altering the structure and behavior of cancer cells. To address the challenges of osteosarcoma (OS), a hi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000864 |
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| author | Arianna Buglione Giulia Alloisio Chiara Ciaccio David Becerril Rodriguez Simone Dogali Marco Luce Stefano Marini Antonio Cricenti Magda Gioia |
| author_facet | Arianna Buglione Giulia Alloisio Chiara Ciaccio David Becerril Rodriguez Simone Dogali Marco Luce Stefano Marini Antonio Cricenti Magda Gioia |
| author_sort | Arianna Buglione |
| collection | DOAJ |
| description | Despite their genetic diversity, metastatic cells converge on similar physical constraints during tumor progression. At the nanoscale, these forces can induce substantial molecular deformations, altering the structure and behavior of cancer cells. To address the challenges of osteosarcoma (OS), a highly aggressive cancer, we explored the mechanobiology of OS cells, in vitro. Using uniaxial-stretching technology, we examined the biophysical modulation of metastatic traits in SAOS-2, U-2 OS, and non-tumorigenic hFOB cells. Changes in cell morphology were quantified using confocal and fluorescence microscopy. To elucidate the molecular mechanisms that translate biomechanical alterations into biochemical responses, we employed Western blotting, real-time quantitative RT-PCR, reactive oxygen species ROS assay, and the mechanosensitive channel blocker Grammostola MechanoToxin4 (GsMTx-4). Our study reveals that mechanical stimulation uniquely affects OS cells, increasing nuclear size and altering the N/C ratio. We found that mechanosensitive (MS) channels are activated, leading to ROS accumulation, Src protein modulation, and histone H3 acetylation. These changes influence OS cell motility and adhesion but not proliferation. Importantly, mechanical preconditioning differentially impacts doxorubicin resistance, correlating with the Src-H3 acetylation axis. This study underscores the critical role of MS channels in OS cells and highlights the importance of mechanobiology in identifying molecular pathways that traditional biochemical approaches may not reveal. Notably, the GsMTx-4 venom peptide effectively countered mechanically induced responses, particularly by inhibiting OS cell migration, without harming healthy cells. Thus, suggesting its potential as a promising therapeutic agent for targeting osteosarcoma metastasis |
| format | Article |
| id | doaj-art-67374175d1d441738f58202a0b61be48 |
| institution | Kabale University |
| issn | 0171-9335 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj-art-67374175d1d441738f58202a0b61be482025-01-23T05:26:14ZengElsevierEuropean Journal of Cell Biology0171-93352025-03-011041151469GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cellsArianna Buglione0Giulia Alloisio1Chiara Ciaccio2David Becerril Rodriguez3Simone Dogali4Marco Luce5Stefano Marini6Antonio Cricenti7Magda Gioia8Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, ItalyInstitute of Structure Matter del Consiglio Nazionale delle Ricerche ISM-CNR, Via del Fosso del Cavaliere 100, Rome I-00133, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, ItalyInstitute of Structure Matter del Consiglio Nazionale delle Ricerche ISM-CNR, Via del Fosso del Cavaliere 100, Rome I-00133, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, ItalyInstitute of Structure Matter del Consiglio Nazionale delle Ricerche ISM-CNR, Via del Fosso del Cavaliere 100, Rome I-00133, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Via Montpellier 1, Roma 00133, Italy; Corresponding author.Despite their genetic diversity, metastatic cells converge on similar physical constraints during tumor progression. At the nanoscale, these forces can induce substantial molecular deformations, altering the structure and behavior of cancer cells. To address the challenges of osteosarcoma (OS), a highly aggressive cancer, we explored the mechanobiology of OS cells, in vitro. Using uniaxial-stretching technology, we examined the biophysical modulation of metastatic traits in SAOS-2, U-2 OS, and non-tumorigenic hFOB cells. Changes in cell morphology were quantified using confocal and fluorescence microscopy. To elucidate the molecular mechanisms that translate biomechanical alterations into biochemical responses, we employed Western blotting, real-time quantitative RT-PCR, reactive oxygen species ROS assay, and the mechanosensitive channel blocker Grammostola MechanoToxin4 (GsMTx-4). Our study reveals that mechanical stimulation uniquely affects OS cells, increasing nuclear size and altering the N/C ratio. We found that mechanosensitive (MS) channels are activated, leading to ROS accumulation, Src protein modulation, and histone H3 acetylation. These changes influence OS cell motility and adhesion but not proliferation. Importantly, mechanical preconditioning differentially impacts doxorubicin resistance, correlating with the Src-H3 acetylation axis. This study underscores the critical role of MS channels in OS cells and highlights the importance of mechanobiology in identifying molecular pathways that traditional biochemical approaches may not reveal. Notably, the GsMTx-4 venom peptide effectively countered mechanically induced responses, particularly by inhibiting OS cell migration, without harming healthy cells. Thus, suggesting its potential as a promising therapeutic agent for targeting osteosarcoma metastasishttp://www.sciencedirect.com/science/article/pii/S0171933524000864MechanobiologyOsteosarcomaCyclic uniaxial stretchMechanosensitive ion channelsGrammostola mechanoToxin 4 (GsMTx-4)Doxorubicin sensitivity |
| spellingShingle | Arianna Buglione Giulia Alloisio Chiara Ciaccio David Becerril Rodriguez Simone Dogali Marco Luce Stefano Marini Antonio Cricenti Magda Gioia GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells European Journal of Cell Biology Mechanobiology Osteosarcoma Cyclic uniaxial stretch Mechanosensitive ion channels Grammostola mechanoToxin 4 (GsMTx-4) Doxorubicin sensitivity |
| title | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| title_full | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| title_fullStr | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| title_full_unstemmed | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| title_short | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| title_sort | gsmtx 4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
| topic | Mechanobiology Osteosarcoma Cyclic uniaxial stretch Mechanosensitive ion channels Grammostola mechanoToxin 4 (GsMTx-4) Doxorubicin sensitivity |
| url | http://www.sciencedirect.com/science/article/pii/S0171933524000864 |
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