Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems
Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2889 |
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| author | Peiyu Wang Renwu Zhou Patrick Thomas Liqian Zhao Rusen Zhou Susmita Mandal Mohit Kumar Jolly Derek J. Richard Bernd H. A. Rehm Kostya (Ken) Ostrikov Xiaofeng Dai Elizabeth D. Williams Erik W. Thompson |
| author_facet | Peiyu Wang Renwu Zhou Patrick Thomas Liqian Zhao Rusen Zhou Susmita Mandal Mohit Kumar Jolly Derek J. Richard Bernd H. A. Rehm Kostya (Ken) Ostrikov Xiaofeng Dai Elizabeth D. Williams Erik W. Thompson |
| author_sort | Peiyu Wang |
| collection | DOAJ |
| description | Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies. The same trend was seen in luminal muscle-invasive bladder cancer model (TSU-Pr1/B1/B2) and the non-muscle-invasive basal 5637 bladder cancer cell line. Three-dimensional spheroid cultures of the bladder cancer cell lines were less sensitive to the PAM treatment compared to their two-dimensional counterparts; however, incrementally better responses were again seen in more mesenchymally-shifted cell lines. This study provides evidence that PAM preferentially inhibits mesenchymally-shifted carcinoma cells, which have been associated with resistance to other therapies. Thus, PAM may represent a novel treatment that can selectively inhibit triple-negative breast cancers and a subset of aggressive bladder cancers, which tend to be more mesenchymal. Our approach may potentially be utilized for other aggressive cancers exhibiting EMT and opens new opportunities for CAP and PAM as a promising new onco-therapy. |
| first_indexed | 2024-03-10T10:33:49Z |
| format | Article |
| id | doaj.art-0fd43a7d48c34df3a344707984779071 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:33:49Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0fd43a7d48c34df3a3447079847790712023-11-21T23:24:32ZengMDPI AGCancers2072-66942021-06-011312288910.3390/cancers13122889Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer SystemsPeiyu Wang0Renwu Zhou1Patrick Thomas2Liqian Zhao3Rusen Zhou4Susmita Mandal5Mohit Kumar Jolly6Derek J. Richard7Bernd H. A. Rehm8Kostya (Ken) Ostrikov9Xiaofeng Dai10Elizabeth D. Williams11Erik W. Thompson12Queensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, AustraliaSchool of Chemical and Biomolecular Engineering, The University of Sydney, Sydney 2006, AustraliaQueensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, AustraliaThe First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, ChinaSchool of Chemical and Biomolecular Engineering, The University of Sydney, Sydney 2006, AustraliaCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, IndiaCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, IndiaQueensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, AustraliaCentre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, AustraliaSchool of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, AustraliaWuxi School of Medicine, Jiangnan University, Wuxi 214122, ChinaQueensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, AustraliaQueensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, AustraliaCold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies. The same trend was seen in luminal muscle-invasive bladder cancer model (TSU-Pr1/B1/B2) and the non-muscle-invasive basal 5637 bladder cancer cell line. Three-dimensional spheroid cultures of the bladder cancer cell lines were less sensitive to the PAM treatment compared to their two-dimensional counterparts; however, incrementally better responses were again seen in more mesenchymally-shifted cell lines. This study provides evidence that PAM preferentially inhibits mesenchymally-shifted carcinoma cells, which have been associated with resistance to other therapies. Thus, PAM may represent a novel treatment that can selectively inhibit triple-negative breast cancers and a subset of aggressive bladder cancers, which tend to be more mesenchymal. Our approach may potentially be utilized for other aggressive cancers exhibiting EMT and opens new opportunities for CAP and PAM as a promising new onco-therapy.https://www.mdpi.com/2072-6694/13/12/2889cold atmospheric plasma (CAP)plasma-activated medium (PAM)epithelial–mesenchymal transition (EMT)reactive oxygen species (ROS) |
| spellingShingle | Peiyu Wang Renwu Zhou Patrick Thomas Liqian Zhao Rusen Zhou Susmita Mandal Mohit Kumar Jolly Derek J. Richard Bernd H. A. Rehm Kostya (Ken) Ostrikov Xiaofeng Dai Elizabeth D. Williams Erik W. Thompson Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems Cancers cold atmospheric plasma (CAP) plasma-activated medium (PAM) epithelial–mesenchymal transition (EMT) reactive oxygen species (ROS) |
| title | Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems |
| title_full | Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems |
| title_fullStr | Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems |
| title_full_unstemmed | Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems |
| title_short | Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems |
| title_sort | epithelial to mesenchymal transition enhances cancer cell sensitivity to cytotoxic effects of cold atmospheric plasmas in breast and bladder cancer systems |
| topic | cold atmospheric plasma (CAP) plasma-activated medium (PAM) epithelial–mesenchymal transition (EMT) reactive oxygen species (ROS) |
| url | https://www.mdpi.com/2072-6694/13/12/2889 |
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