- The cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP. Subsequent alterations in viability, proliferation, and phenotype were analyzed via flow cytometry and metabolic alterations by Seahorse Cell Mito Stress Tests. It was found that cells generally exhibited reduced viability and proliferation, stemming from CAP induced G2/M cell cycle arrest and subsequent apoptosis, as well as increased mitochondrial stress following CAP treatment. Overall, sensitivity to CAP treatment was found to be cell type dependent with T cells being the most affected. Interestingly, CAP influenced the polarization of M0 macrophages to a “M0/M2-like” phenotype, and M1 macrophages were found to display a heightened sensitivity to CAP induced mitochondrial stress. CAP also inhibited the growth and killed melanoma cells in 2D and 3D in vitro cell culture models in a dose-dependent manner. Improving our understanding of oxidative stress, mechanisms to manipulate it, and its implications for the tumor microenvironment may help in the discovery of new therapeutic targets.
MetadatenAuthor: | Emily R. Trzeciak, Niklas Zimmer, Isabelle Marie-Sophie GehringerGND, Lara Stein, Barbara Graefen, Jonathan SchuppGND, Achim Stephan, Stephan RietzGND, Michael PrantnerORCiD, Andrea TüttenbergORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-831367 |
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DOI: | https://doi.org/10.3390/cells11060930 |
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ISSN: | 2073-4409 |
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Parent Title (English): | Cells |
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Publisher: | MDPI |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2022/03/08 |
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Date of first Publication: | 2022/03/08 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2024/06/25 |
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Tag: | T cell; cold atmospheric plasma; macrophage; malignant melanoma; metabolic alterations; plasma jet; tumor microenvironment; tumor spheroids; tumor therapy |
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Volume: | 11 |
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Issue: | 6, art. 930 |
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Article Number: | 930 |
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Page Number: | 31 |
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First Page: | 1 |
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Last Page: | 31 |
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Note: | Funding: Wilhelm Sander Foundation ; 2020.132.1 |
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Note: | Funding: Hiege Foundation ; 200504 |
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Note: | Funding: Hiege Foundation ; CRC1066 |
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Note: | Funding: CRC1066 |
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Note: | Funding: DAAD One-Year Research Grant for Doctoral Candidates ; 57552339 |
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Note: | Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3390/cells11060930/s1, Figure S1: Gating strategies, Figure S2: MiniJet-R and intracellular ROS quantification, Figure S3: UKRV-Mel-15a cell cycle and cell death data, Figure S4: Non-significant macrophage polarization markers, Figure S5: Example Seahorse OCR and ECAR data, Figure S6: UKRV-Mel-15a antioxidant data. |
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HeBIS-PPN: | 522325491 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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