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Cisplatin induces stemness in ovarian cancer
The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renew...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058697/ https://www.ncbi.nlm.nih.gov/pubmed/27105520 http://dx.doi.org/10.18632/oncotarget.8852 |
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author | Wiechert, Andrew Saygin, Caner Thiagarajan, Praveena S. Rao, Vinay S. Hale, James S. Gupta, Nikhil Hitomi, Masahiro Nagaraj, Anil Belur DiFeo, Analisa Lathia, Justin D. Reizes, Ofer |
author_facet | Wiechert, Andrew Saygin, Caner Thiagarajan, Praveena S. Rao, Vinay S. Hale, James S. Gupta, Nikhil Hitomi, Masahiro Nagaraj, Anil Belur DiFeo, Analisa Lathia, Justin D. Reizes, Ofer |
author_sort | Wiechert, Andrew |
collection | PubMed |
description | The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility. |
format | Online Article Text |
id | pubmed-5058697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50586972016-10-15 Cisplatin induces stemness in ovarian cancer Wiechert, Andrew Saygin, Caner Thiagarajan, Praveena S. Rao, Vinay S. Hale, James S. Gupta, Nikhil Hitomi, Masahiro Nagaraj, Anil Belur DiFeo, Analisa Lathia, Justin D. Reizes, Ofer Oncotarget Research Paper The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility. Impact Journals LLC 2016-04-20 /pmc/articles/PMC5058697/ /pubmed/27105520 http://dx.doi.org/10.18632/oncotarget.8852 Text en Copyright: © 2016 Wiechert et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wiechert, Andrew Saygin, Caner Thiagarajan, Praveena S. Rao, Vinay S. Hale, James S. Gupta, Nikhil Hitomi, Masahiro Nagaraj, Anil Belur DiFeo, Analisa Lathia, Justin D. Reizes, Ofer Cisplatin induces stemness in ovarian cancer |
title | Cisplatin induces stemness in ovarian cancer |
title_full | Cisplatin induces stemness in ovarian cancer |
title_fullStr | Cisplatin induces stemness in ovarian cancer |
title_full_unstemmed | Cisplatin induces stemness in ovarian cancer |
title_short | Cisplatin induces stemness in ovarian cancer |
title_sort | cisplatin induces stemness in ovarian cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058697/ https://www.ncbi.nlm.nih.gov/pubmed/27105520 http://dx.doi.org/10.18632/oncotarget.8852 |
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