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...
Gespeichert in:
Veröffentlicht in: | European journal of cell biology 2024-12, Vol.104 (1), p.151469, Article 151469 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 1 |
container_start_page | 151469 |
container_title | European journal of cell biology |
container_volume | 104 |
creator | Buglione, Arianna Alloisio, Giulia Ciaccio, Chiara Rodriguez, David Becerril Dogali, Simone Luce, Marco Marini, Stefano Cricenti, Antonio Gioia, Magda |
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
[Display omitted]
•The Pivotal Role of Mechanosensitive Channels in Modulating Osteosarcoma Cell Behavior.•Mechanosensitive Channels Drive SRC-histone H3 Acetylation Axis and Doxorubicin Resistance in Osteosarcoma Cells.•GsTMx-4 venom peptide effectively antagonize the mechanically induced changes without harming healthy cells. |
doi_str_mv | 10.1016/j.ejcb.2024.151469 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_3146710055</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0171933524000864</els_id><sourcerecordid>3146710055</sourcerecordid><originalsourceid>FETCH-LOGICAL-e1539-6375a2298c98b0ebe2d5dd9aa64dc2c468ade70f0e0f99a0b07c84142de631a03</originalsourceid><addsrcrecordid>eNo1kU1PwzAMhiMEgjH4AxxQjlw64qZfkbigCQYSiAucIzfxIFPbjCadGL-eThsny_Jj65Ufxq5AzEBAcbua0crUs1Sk2QxyyAp1xCZQQJVAqqpjNhFQQqKkzM_YeQgrISCvlDplZ1IVJZRlNmGfi_D6_pNkfEOdb3n0P67j2EX89J37pcBr59df2-AMNrz1dmgwOt9xv-QtRQxxbA2PPboY-Lj6NbQ4TkMkH7A3vkVuqGnCBTtZYhPo8lCn7OPx4X3-lLy8LZ7n9y8JQS5VUsgyx3RMb1RVC6optbm1CrHIrElNVlRoqRRLQWKpFIpalKbKIEstFRJQyCm72d9d9_57oBB168IuAXbkh6Dl-KYShMjzEb0-oEPdktXr3rXYb_X_c0bgbg_QGHjjqNfBOOoMWdeTidp6p0HonQu90jsXeudC713IPzfPfYY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3146710055</pqid></control><display><type>article</type><title>GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells</title><source>Elsevier ScienceDirect Journals Complete</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Buglione, Arianna ; Alloisio, Giulia ; Ciaccio, Chiara ; Rodriguez, David Becerril ; Dogali, Simone ; Luce, Marco ; Marini, Stefano ; Cricenti, Antonio ; Gioia, Magda</creator><creatorcontrib>Buglione, Arianna ; Alloisio, Giulia ; Ciaccio, Chiara ; Rodriguez, David Becerril ; Dogali, Simone ; Luce, Marco ; Marini, Stefano ; Cricenti, Antonio ; Gioia, Magda</creatorcontrib><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
[Display omitted]
•The Pivotal Role of Mechanosensitive Channels in Modulating Osteosarcoma Cell Behavior.•Mechanosensitive Channels Drive SRC-histone H3 Acetylation Axis and Doxorubicin Resistance in Osteosarcoma Cells.•GsTMx-4 venom peptide effectively antagonize the mechanically induced changes without harming healthy cells.</description><identifier>ISSN: 0171-9335</identifier><identifier>ISSN: 1618-1298</identifier><identifier>EISSN: 1618-1298</identifier><identifier>DOI: 10.1016/j.ejcb.2024.151469</identifier><identifier>PMID: 39671774</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Cell migration ; Cyclic uniaxial stretch ; Doxorubicin sensitivity ; Grammostola mechanoToxin 4 (GsMTx-4) ; Mechanobiology ; Mechanosensitive ion channels ; Osteosarcoma</subject><ispartof>European journal of cell biology, 2024-12, Vol.104 (1), p.151469, Article 151469</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejcb.2024.151469$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,864,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39671774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buglione, Arianna</creatorcontrib><creatorcontrib>Alloisio, Giulia</creatorcontrib><creatorcontrib>Ciaccio, Chiara</creatorcontrib><creatorcontrib>Rodriguez, David Becerril</creatorcontrib><creatorcontrib>Dogali, Simone</creatorcontrib><creatorcontrib>Luce, Marco</creatorcontrib><creatorcontrib>Marini, Stefano</creatorcontrib><creatorcontrib>Cricenti, Antonio</creatorcontrib><creatorcontrib>Gioia, Magda</creatorcontrib><title>GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells</title><title>European journal of cell biology</title><addtitle>Eur J Cell Biol</addtitle><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
[Display omitted]
•The Pivotal Role of Mechanosensitive Channels in Modulating Osteosarcoma Cell Behavior.•Mechanosensitive Channels Drive SRC-histone H3 Acetylation Axis and Doxorubicin Resistance in Osteosarcoma Cells.•GsTMx-4 venom peptide effectively antagonize the mechanically induced changes without harming healthy cells.</description><subject>Cell migration</subject><subject>Cyclic uniaxial stretch</subject><subject>Doxorubicin sensitivity</subject><subject>Grammostola mechanoToxin 4 (GsMTx-4)</subject><subject>Mechanobiology</subject><subject>Mechanosensitive ion channels</subject><subject>Osteosarcoma</subject><issn>0171-9335</issn><issn>1618-1298</issn><issn>1618-1298</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNo1kU1PwzAMhiMEgjH4AxxQjlw64qZfkbigCQYSiAucIzfxIFPbjCadGL-eThsny_Jj65Ufxq5AzEBAcbua0crUs1Sk2QxyyAp1xCZQQJVAqqpjNhFQQqKkzM_YeQgrISCvlDplZ1IVJZRlNmGfi_D6_pNkfEOdb3n0P67j2EX89J37pcBr59df2-AMNrz1dmgwOt9xv-QtRQxxbA2PPboY-Lj6NbQ4TkMkH7A3vkVuqGnCBTtZYhPo8lCn7OPx4X3-lLy8LZ7n9y8JQS5VUsgyx3RMb1RVC6optbm1CrHIrElNVlRoqRRLQWKpFIpalKbKIEstFRJQyCm72d9d9_57oBB168IuAXbkh6Dl-KYShMjzEb0-oEPdktXr3rXYb_X_c0bgbg_QGHjjqNfBOOoMWdeTidp6p0HonQu90jsXeudC713IPzfPfYY</recordid><startdate>20241211</startdate><enddate>20241211</enddate><creator>Buglione, Arianna</creator><creator>Alloisio, Giulia</creator><creator>Ciaccio, Chiara</creator><creator>Rodriguez, David Becerril</creator><creator>Dogali, Simone</creator><creator>Luce, Marco</creator><creator>Marini, Stefano</creator><creator>Cricenti, Antonio</creator><creator>Gioia, Magda</creator><general>Elsevier GmbH</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20241211</creationdate><title>GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells</title><author>Buglione, Arianna ; Alloisio, Giulia ; Ciaccio, Chiara ; Rodriguez, David Becerril ; Dogali, Simone ; Luce, Marco ; Marini, Stefano ; Cricenti, Antonio ; Gioia, Magda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e1539-6375a2298c98b0ebe2d5dd9aa64dc2c468ade70f0e0f99a0b07c84142de631a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cell migration</topic><topic>Cyclic uniaxial stretch</topic><topic>Doxorubicin sensitivity</topic><topic>Grammostola mechanoToxin 4 (GsMTx-4)</topic><topic>Mechanobiology</topic><topic>Mechanosensitive ion channels</topic><topic>Osteosarcoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buglione, Arianna</creatorcontrib><creatorcontrib>Alloisio, Giulia</creatorcontrib><creatorcontrib>Ciaccio, Chiara</creatorcontrib><creatorcontrib>Rodriguez, David Becerril</creatorcontrib><creatorcontrib>Dogali, Simone</creatorcontrib><creatorcontrib>Luce, Marco</creatorcontrib><creatorcontrib>Marini, Stefano</creatorcontrib><creatorcontrib>Cricenti, Antonio</creatorcontrib><creatorcontrib>Gioia, Magda</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buglione, Arianna</au><au>Alloisio, Giulia</au><au>Ciaccio, Chiara</au><au>Rodriguez, David Becerril</au><au>Dogali, Simone</au><au>Luce, Marco</au><au>Marini, Stefano</au><au>Cricenti, Antonio</au><au>Gioia, Magda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells</atitle><jtitle>European journal of cell biology</jtitle><addtitle>Eur J Cell Biol</addtitle><date>2024-12-11</date><risdate>2024</risdate><volume>104</volume><issue>1</issue><spage>151469</spage><pages>151469-</pages><artnum>151469</artnum><issn>0171-9335</issn><issn>1618-1298</issn><eissn>1618-1298</eissn><abstract>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
[Display omitted]
•The Pivotal Role of Mechanosensitive Channels in Modulating Osteosarcoma Cell Behavior.•Mechanosensitive Channels Drive SRC-histone H3 Acetylation Axis and Doxorubicin Resistance in Osteosarcoma Cells.•GsTMx-4 venom peptide effectively antagonize the mechanically induced changes without harming healthy cells.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>39671774</pmid><doi>10.1016/j.ejcb.2024.151469</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0171-9335 |
ispartof | European journal of cell biology, 2024-12, Vol.104 (1), p.151469, Article 151469 |
issn | 0171-9335 1618-1298 1618-1298 |
language | eng |
recordid | cdi_proquest_miscellaneous_3146710055 |
source | Elsevier ScienceDirect Journals Complete; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals |
subjects | Cell migration Cyclic uniaxial stretch Doxorubicin sensitivity Grammostola mechanoToxin 4 (GsMTx-4) Mechanobiology Mechanosensitive ion channels Osteosarcoma |
title | GsMTx-4 venom toxin antagonizes biophysical modulation of metastatic traits in human osteosarcoma cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T04%3A36%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GsMTx-4%20venom%20toxin%20antagonizes%20biophysical%20modulation%20of%20metastatic%20traits%20in%20human%20osteosarcoma%20cells&rft.jtitle=European%20journal%20of%20cell%20biology&rft.au=Buglione,%20Arianna&rft.date=2024-12-11&rft.volume=104&rft.issue=1&rft.spage=151469&rft.pages=151469-&rft.artnum=151469&rft.issn=0171-9335&rft.eissn=1618-1298&rft_id=info:doi/10.1016/j.ejcb.2024.151469&rft_dat=%3Cproquest_pubme%3E3146710055%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3146710055&rft_id=info:pmid/39671774&rft_els_id=S0171933524000864&rfr_iscdi=true |