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Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells

Recently, a subpopulation of tumor cells, called cancer stem cells (CSC), has been characterized, and these have emerged as a major topic in cancer research. CSC are proposed to repair DNA damage more efficiently than the rest of tumor cells, resisting chemotherapy or radiotherapy and causing clinic...

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Autores principales: Valencia-González, Heriberto Abraham, Ruíz, Graciela, Ortiz-Sánchez, Elizabeth, García-Carrancá, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470433/
https://www.ncbi.nlm.nih.gov/pubmed/31073313
http://dx.doi.org/10.1155/2019/7038953
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author Valencia-González, Heriberto Abraham
Ruíz, Graciela
Ortiz-Sánchez, Elizabeth
García-Carrancá, Alejandro
author_facet Valencia-González, Heriberto Abraham
Ruíz, Graciela
Ortiz-Sánchez, Elizabeth
García-Carrancá, Alejandro
author_sort Valencia-González, Heriberto Abraham
collection PubMed
description Recently, a subpopulation of tumor cells, called cancer stem cells (CSC), has been characterized, and these have emerged as a major topic in cancer research. CSC are proposed to repair DNA damage more efficiently than the rest of tumor cells, resisting chemotherapy or radiotherapy and causing clinical recurrence and metastasis. We aimed to determine the molecular basis of radioresistance and first compared the response to ionizing radiation (IR) between cancer stem cell-enriched cultures grown as spheres and conventional tumor cell line cultures grown as monolayer, from HeLa and MCF-7 cancer cell lines. To verify that our sphere cultures were enriched in CSC, we evaluated the double staining of CD49f and ALDH activity for HeLa cells by flow cytometry. We then evaluated whether differences could exist in sensor elements in the DNA damage response pathway among these cultures. We found that CSC cultures showed less sensitivity to radiation than conventional tumor cell line cultures. We observed a higher baseline expression of activated response sensor proteins of DNA damage, such as ATM, H2A.X, and PARP1, in untreated CSC cultures. These findings provide the first evidence, to our knowledge, that DNA damage response sensor proteins are present and preferentially activated in CSC, as opposed to the bulk of cells in monolayer cultures. Likewise, they provide the basis for biological differences in response to IR between CSC and other tumor cell populations. Understanding the DNA damage response pathway may provide therapeutic targets to sensitize CSC to cytotoxic therapies to improve current cancer treatments.
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spelling pubmed-64704332019-05-09 Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells Valencia-González, Heriberto Abraham Ruíz, Graciela Ortiz-Sánchez, Elizabeth García-Carrancá, Alejandro Stem Cells Int Research Article Recently, a subpopulation of tumor cells, called cancer stem cells (CSC), has been characterized, and these have emerged as a major topic in cancer research. CSC are proposed to repair DNA damage more efficiently than the rest of tumor cells, resisting chemotherapy or radiotherapy and causing clinical recurrence and metastasis. We aimed to determine the molecular basis of radioresistance and first compared the response to ionizing radiation (IR) between cancer stem cell-enriched cultures grown as spheres and conventional tumor cell line cultures grown as monolayer, from HeLa and MCF-7 cancer cell lines. To verify that our sphere cultures were enriched in CSC, we evaluated the double staining of CD49f and ALDH activity for HeLa cells by flow cytometry. We then evaluated whether differences could exist in sensor elements in the DNA damage response pathway among these cultures. We found that CSC cultures showed less sensitivity to radiation than conventional tumor cell line cultures. We observed a higher baseline expression of activated response sensor proteins of DNA damage, such as ATM, H2A.X, and PARP1, in untreated CSC cultures. These findings provide the first evidence, to our knowledge, that DNA damage response sensor proteins are present and preferentially activated in CSC, as opposed to the bulk of cells in monolayer cultures. Likewise, they provide the basis for biological differences in response to IR between CSC and other tumor cell populations. Understanding the DNA damage response pathway may provide therapeutic targets to sensitize CSC to cytotoxic therapies to improve current cancer treatments. Hindawi 2019-04-03 /pmc/articles/PMC6470433/ /pubmed/31073313 http://dx.doi.org/10.1155/2019/7038953 Text en Copyright © 2019 Heriberto Abraham Valencia-González et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Valencia-González, Heriberto Abraham
Ruíz, Graciela
Ortiz-Sánchez, Elizabeth
García-Carrancá, Alejandro
Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title_full Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title_fullStr Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title_full_unstemmed Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title_short Cancer Stem Cells from Tumor Cell Lines Activate the DNA Damage Response Pathway after Ionizing Radiation More Efficiently Than Noncancer Stem Cells
title_sort cancer stem cells from tumor cell lines activate the dna damage response pathway after ionizing radiation more efficiently than noncancer stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470433/
https://www.ncbi.nlm.nih.gov/pubmed/31073313
http://dx.doi.org/10.1155/2019/7038953
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