α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis.
Epidermal human keratinocytes are exposed to a wide range of environmental genotoxic insults, including the UV component of solar radiation. Epidermal homeostasis in response to cellular or tissue damage is maintained by a population of keratinocyte stem cells (KSC) that reside in the basal layer of...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0046968 |
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| _version_ | 1850224595974488064 |
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| author | Helen Wray Ian C Mackenzie Alan Storey Harshad Navsaria |
| author_facet | Helen Wray Ian C Mackenzie Alan Storey Harshad Navsaria |
| author_sort | Helen Wray |
| collection | DOAJ |
| description | Epidermal human keratinocytes are exposed to a wide range of environmental genotoxic insults, including the UV component of solar radiation. Epidermal homeostasis in response to cellular or tissue damage is maintained by a population of keratinocyte stem cells (KSC) that reside in the basal layer of the epithelium. Using cell sorting based on cell-surface markers, we have identified a novel α6 integrin(high+)/CD44(+) sub-population of basal keratinocytes. These α6 integrin(high+)/CD44(+) keratinocytes have both high proliferative potential, form colonies in culture that have characteristics of holoclones and have a unique pattern of resistance to apoptosis induced by UVB radiation or by agents that induce single- or double strand DNA breaks. Resistance to UVB induced apoptosis in the α6 integrin(high+)/CD44(+) cells involved increased expression of TAp63 and was overcome by PI-3 kinase inhibition. In marked contrast, the α6 integrin(high+)/CD44(+) cells were sensitive to apoptosis induced by the cross-linking agent cisplatin, and imatinib inhibition of c-Abl blocked the ability of cisplatin to kill α6 integrin(high+)/CD44(+) cells. Our findings reveal a population of basal keratinocytes with long-term proliferative properties that display specific patterns of apoptotic resistance that is dependent upon the genotoxic stimulus, and provide insights into how these cells can be targeted with chemotherapeutic agents. |
| format | Article |
| id | doaj-art-482ba8d8b89c4769ac6d7f33be54f2d8 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-482ba8d8b89c4769ac6d7f33be54f2d82025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4696810.1371/journal.pone.0046968α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis.Helen WrayIan C MackenzieAlan StoreyHarshad NavsariaEpidermal human keratinocytes are exposed to a wide range of environmental genotoxic insults, including the UV component of solar radiation. Epidermal homeostasis in response to cellular or tissue damage is maintained by a population of keratinocyte stem cells (KSC) that reside in the basal layer of the epithelium. Using cell sorting based on cell-surface markers, we have identified a novel α6 integrin(high+)/CD44(+) sub-population of basal keratinocytes. These α6 integrin(high+)/CD44(+) keratinocytes have both high proliferative potential, form colonies in culture that have characteristics of holoclones and have a unique pattern of resistance to apoptosis induced by UVB radiation or by agents that induce single- or double strand DNA breaks. Resistance to UVB induced apoptosis in the α6 integrin(high+)/CD44(+) cells involved increased expression of TAp63 and was overcome by PI-3 kinase inhibition. In marked contrast, the α6 integrin(high+)/CD44(+) cells were sensitive to apoptosis induced by the cross-linking agent cisplatin, and imatinib inhibition of c-Abl blocked the ability of cisplatin to kill α6 integrin(high+)/CD44(+) cells. Our findings reveal a population of basal keratinocytes with long-term proliferative properties that display specific patterns of apoptotic resistance that is dependent upon the genotoxic stimulus, and provide insights into how these cells can be targeted with chemotherapeutic agents.https://doi.org/10.1371/journal.pone.0046968 |
| spellingShingle | Helen Wray Ian C Mackenzie Alan Storey Harshad Navsaria α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. PLoS ONE |
| title | α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. |
| title_full | α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. |
| title_fullStr | α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. |
| title_full_unstemmed | α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. |
| title_short | α6 Integrin and CD44 enrich for a primary keratinocyte population that displays resistance to UV-induced apoptosis. |
| title_sort | α6 integrin and cd44 enrich for a primary keratinocyte population that displays resistance to uv induced apoptosis |
| url | https://doi.org/10.1371/journal.pone.0046968 |
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