Oxygen levels do not determine radiation survival of breast cancer stem cells.
For more than a century oxygen has been known to be one of the most powerful radiosensitizers. However, despite decades of preclinical and clinical research aimed at overcoming tumor hypoxia, little clinical progress has been made so far. Ionizing radiation damages DNA through generation of free rad...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3315542?pdf=render |
| _version_ | 1819138766397243392 |
|---|---|
| author | Chann Lagadec Carmen Dekmezian Lucile Bauché Frank Pajonk |
| author_facet | Chann Lagadec Carmen Dekmezian Lucile Bauché Frank Pajonk |
| author_sort | Chann Lagadec |
| collection | DOAJ |
| description | For more than a century oxygen has been known to be one of the most powerful radiosensitizers. However, despite decades of preclinical and clinical research aimed at overcoming tumor hypoxia, little clinical progress has been made so far. Ionizing radiation damages DNA through generation of free radicals. In the presence of oxygen these lesions are chemically modified, and thus harder to repair while hypoxia protects cells from radiation (Oxygen enhancement ratio (OER)). Breast cancer stem cells (BSCSs) are protected from radiation by high levels of free radical scavengers even in the presence of oxygen. This led us to hypothesize that BCSCs exhibit an OER of 1. Using four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, SUM159PT) and primary breast cancer samples, we determined the number of BCSCs using cancer stem cell markers (ALDH1, low proteasome activity), compared radiation clonogenic survival and mammosphere formation under normoxic and hypoxic conditions, and correlated these results to the expression levels of key members of the free radical scavenging systems. The number of BCSCs increased with increased aggressiveness of the cancer. This correlated with increased radioresistance (SF(8Gy)), and decreasing OERs. When cultured as mammospheres, breast cancer cell lines and primary samples were highly radioresistant and not further protected by hypoxia (OER∼1).We conclude that because BCSCs are protected from radiation through high expression levels of free radical scavengers, hypoxia does not lead to additional radioprotection of BCSCs. |
| first_indexed | 2024-12-22T11:11:59Z |
| format | Article |
| id | doaj.art-89276b172852469191cb768e22c6b8fd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:11:59Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-89276b172852469191cb768e22c6b8fd2022-12-21T18:28:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3454510.1371/journal.pone.0034545Oxygen levels do not determine radiation survival of breast cancer stem cells.Chann LagadecCarmen DekmezianLucile BauchéFrank PajonkFor more than a century oxygen has been known to be one of the most powerful radiosensitizers. However, despite decades of preclinical and clinical research aimed at overcoming tumor hypoxia, little clinical progress has been made so far. Ionizing radiation damages DNA through generation of free radicals. In the presence of oxygen these lesions are chemically modified, and thus harder to repair while hypoxia protects cells from radiation (Oxygen enhancement ratio (OER)). Breast cancer stem cells (BSCSs) are protected from radiation by high levels of free radical scavengers even in the presence of oxygen. This led us to hypothesize that BCSCs exhibit an OER of 1. Using four established breast cancer cell lines (MCF-7, T47D, MDA-MB-231, SUM159PT) and primary breast cancer samples, we determined the number of BCSCs using cancer stem cell markers (ALDH1, low proteasome activity), compared radiation clonogenic survival and mammosphere formation under normoxic and hypoxic conditions, and correlated these results to the expression levels of key members of the free radical scavenging systems. The number of BCSCs increased with increased aggressiveness of the cancer. This correlated with increased radioresistance (SF(8Gy)), and decreasing OERs. When cultured as mammospheres, breast cancer cell lines and primary samples were highly radioresistant and not further protected by hypoxia (OER∼1).We conclude that because BCSCs are protected from radiation through high expression levels of free radical scavengers, hypoxia does not lead to additional radioprotection of BCSCs.http://europepmc.org/articles/PMC3315542?pdf=render |
| spellingShingle | Chann Lagadec Carmen Dekmezian Lucile Bauché Frank Pajonk Oxygen levels do not determine radiation survival of breast cancer stem cells. PLoS ONE |
| title | Oxygen levels do not determine radiation survival of breast cancer stem cells. |
| title_full | Oxygen levels do not determine radiation survival of breast cancer stem cells. |
| title_fullStr | Oxygen levels do not determine radiation survival of breast cancer stem cells. |
| title_full_unstemmed | Oxygen levels do not determine radiation survival of breast cancer stem cells. |
| title_short | Oxygen levels do not determine radiation survival of breast cancer stem cells. |
| title_sort | oxygen levels do not determine radiation survival of breast cancer stem cells |
| url | http://europepmc.org/articles/PMC3315542?pdf=render |
| work_keys_str_mv | AT channlagadec oxygenlevelsdonotdetermineradiationsurvivalofbreastcancerstemcells AT carmendekmezian oxygenlevelsdonotdetermineradiationsurvivalofbreastcancerstemcells AT lucilebauche oxygenlevelsdonotdetermineradiationsurvivalofbreastcancerstemcells AT frankpajonk oxygenlevelsdonotdetermineradiationsurvivalofbreastcancerstemcells |