TY  - JOUR
A1  - Trzeciak, Emily R.
A1  - Zimmer, Niklas
A1  - Gehringer, Isabelle Marie-Sophie
A1  - Stein, Lara
A1  - Graefen, Barbara
A1  - Schupp, Jonathan
A1  - Stephan, Achim
A1  - Rietz, Stephan
A1  - Prantner, Michael
A1  - Tüttenberg, Andrea
T1  - Oxidative stress differentially influences the survival and metabolism of cells in the melanoma microenvironment
T2  - Cells
N2  - 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.
KW  - tumor microenvironment
KW  - metabolic alterations
KW  - tumor therapy
KW  - cold atmospheric plasma
KW  - tumor spheroids
KW  - plasma jet
KW  - malignant melanoma
KW  - T cell
KW  - macrophage
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83136
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-831367
SN  - 2073-4409
N1  - Funding: Wilhelm Sander Foundation ; 2020.132.1
N1  - Funding: Hiege Foundation ; 200504
N1  - Funding: Hiege Foundation ; CRC1066
N1  - Funding: CRC1066
N1  - Funding: DAAD One-Year Research Grant for Doctoral Candidates ; 57552339
N1  - 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.
VL  - 11
IS  - 6, art. 930
SP  - 1
EP  - 31
PB  - MDPI
CY  - Basel
ER  -