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Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay
Slow-cycling cancer cells (SCC) contribute to the aggressiveness of many cancers, and their invasiveness and chemoresistance pose a great therapeutic challenge. However, in melanoma, their tumor-initiating abilities are not fully understood. In this study, we used the syngeneic transplantation assay...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798190/ https://www.ncbi.nlm.nih.gov/pubmed/36563633 http://dx.doi.org/10.1016/j.neo.2022.100865 |
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author | Kusienicka, Anna Cieśla, Maciej Bukowska-Strakova, Karolina Nowak, Witold Norbert Bronisz-Budzyńska, Iwona Seretny, Agnieszka Żukowska, Monika Jeż, Mateusz Wolnik, Jan Józkowicz, Alicja |
author_facet | Kusienicka, Anna Cieśla, Maciej Bukowska-Strakova, Karolina Nowak, Witold Norbert Bronisz-Budzyńska, Iwona Seretny, Agnieszka Żukowska, Monika Jeż, Mateusz Wolnik, Jan Józkowicz, Alicja |
author_sort | Kusienicka, Anna |
collection | PubMed |
description | Slow-cycling cancer cells (SCC) contribute to the aggressiveness of many cancers, and their invasiveness and chemoresistance pose a great therapeutic challenge. However, in melanoma, their tumor-initiating abilities are not fully understood. In this study, we used the syngeneic transplantation assay to investigate the tumor-initiating properties of melanoma SCC in the physiologically relevant in vivo settings. For this we used B16-F10 murine melanoma cell line where we identified a small fraction of SCC. We found that, unlike human melanoma, the murine melanoma SCC were not marked by the high expression of the epigenetic enzyme Jarid1b. At the same time, their slow-cycling phenotype was a temporary state, similar to what was described in human melanoma. Progeny of SCC had slightly increased doxorubicin resistance and altered expression of melanogenesis genes, independent of the expression of cancer stem cell markers. Single-cell expansion of SCC revealed delayed growth and reduced clone formation when compared to non-SCC, which was further confirmed by an in vitro limiting dilution assay. Finally, syngeneic transplantation of 10 cells in vivo established that SCC were able to initiate growth in primary recipients and continue growth in the serial transplantation assay, suggesting their self-renewal nature. Together, our study highlights the high plasticity and tumorigenicity of murine melanoma SCC and suggests their role in melanoma aggressiveness. |
format | Online Article Text |
id | pubmed-9798190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97981902022-12-30 Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay Kusienicka, Anna Cieśla, Maciej Bukowska-Strakova, Karolina Nowak, Witold Norbert Bronisz-Budzyńska, Iwona Seretny, Agnieszka Żukowska, Monika Jeż, Mateusz Wolnik, Jan Józkowicz, Alicja Neoplasia Original Research Slow-cycling cancer cells (SCC) contribute to the aggressiveness of many cancers, and their invasiveness and chemoresistance pose a great therapeutic challenge. However, in melanoma, their tumor-initiating abilities are not fully understood. In this study, we used the syngeneic transplantation assay to investigate the tumor-initiating properties of melanoma SCC in the physiologically relevant in vivo settings. For this we used B16-F10 murine melanoma cell line where we identified a small fraction of SCC. We found that, unlike human melanoma, the murine melanoma SCC were not marked by the high expression of the epigenetic enzyme Jarid1b. At the same time, their slow-cycling phenotype was a temporary state, similar to what was described in human melanoma. Progeny of SCC had slightly increased doxorubicin resistance and altered expression of melanogenesis genes, independent of the expression of cancer stem cell markers. Single-cell expansion of SCC revealed delayed growth and reduced clone formation when compared to non-SCC, which was further confirmed by an in vitro limiting dilution assay. Finally, syngeneic transplantation of 10 cells in vivo established that SCC were able to initiate growth in primary recipients and continue growth in the serial transplantation assay, suggesting their self-renewal nature. Together, our study highlights the high plasticity and tumorigenicity of murine melanoma SCC and suggests their role in melanoma aggressiveness. Neoplasia Press 2022-12-21 /pmc/articles/PMC9798190/ /pubmed/36563633 http://dx.doi.org/10.1016/j.neo.2022.100865 Text en © 2022 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Kusienicka, Anna Cieśla, Maciej Bukowska-Strakova, Karolina Nowak, Witold Norbert Bronisz-Budzyńska, Iwona Seretny, Agnieszka Żukowska, Monika Jeż, Mateusz Wolnik, Jan Józkowicz, Alicja Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title | Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title_full | Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title_fullStr | Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title_full_unstemmed | Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title_short | Slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
title_sort | slow-cycling murine melanoma cells display plasticity and enhanced tumorigenicity in syngeneic transplantation assay |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798190/ https://www.ncbi.nlm.nih.gov/pubmed/36563633 http://dx.doi.org/10.1016/j.neo.2022.100865 |
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