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Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells
BACKGROUND: The association of cancer stem cells with epithelial–mesenchymal transition (EMT) is receiving attention. We found in our previous study that EMT existed from CD24− phenotype cells to their differentiated cells. It was shown that cyclin D1 functioned in sustaining self-renewal independen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699300/ https://www.ncbi.nlm.nih.gov/pubmed/23836980 http://dx.doi.org/10.2147/OTT.S44177 |
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author | Jiao, Jie Huang, Lu Ye, Feng Shi, MinFeng Cheng, XiaoDong Wang, XinYu Hu, DongXiao Xie, Xing Lu, WeiGuo |
author_facet | Jiao, Jie Huang, Lu Ye, Feng Shi, MinFeng Cheng, XiaoDong Wang, XinYu Hu, DongXiao Xie, Xing Lu, WeiGuo |
author_sort | Jiao, Jie |
collection | PubMed |
description | BACKGROUND: The association of cancer stem cells with epithelial–mesenchymal transition (EMT) is receiving attention. We found in our previous study that EMT existed from CD24− phenotype cells to their differentiated cells. It was shown that cyclin D1 functioned in sustaining self-renewal independent of CDK4/CDK6 activation, but its effect on the EMT mechanism in ovarian cancer stem cells is unclear. METHODS: The anchorage-independent spheroids from ovarian adenocarcinoma cell line 3AO were formed in a serum-free medium. CD24− and CD24+ cells were isolated by fluorescence-activated cell sorting. Cell morphology, viability, apoptosis, and migratory ability were observed. Stem-related molecule Bmi-1, Oct-4 and EMT-related marker E-cadherin, and vimentin expressions were analyzed. Cyclin D1 expression in CD24− phenotype enriched spheroids was knocked down with small interfering RNA, and its effects on cell proliferation, apoptosis, migration ability, and EMT-related phenotype after transfection were observed. RESULTS: In our study, CD24− cells presented stronger proliferative, anti-apoptosis capacity, and migratory ability, than CD24+ cells or parental cells. CD24− cells grew with a scattered spindle-shape within 3 days of culture and transformed into a cobblestone-like shape, identical to CD24+ cells or parental cells at 7 days of culture. CD24− cells or spheroids highly expressed cyclin D1, Bmi-1, and vimentin, and seldom expressed E-cadherin, while CD24+ or parental cells showed the opposite expression. Furthermore, cyclin D1-targeted small interfering RNA resulted in decreased vimentin expression in spheroids. Transfected cells also exhibited an obvious decrease in cell viability and migration, but an increase in cell apoptosis. CONCLUSION: Cancer stem cell-like cells possess mesenchymal characteristics and EMT ability, and cyclin D1 involves in EMT mechanism, suggesting that EMT of cancer stem cell-like cells may play a key role in invasion and metastasis of ovarian cancer. |
format | Online Article Text |
id | pubmed-3699300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36993002013-07-08 Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells Jiao, Jie Huang, Lu Ye, Feng Shi, MinFeng Cheng, XiaoDong Wang, XinYu Hu, DongXiao Xie, Xing Lu, WeiGuo Onco Targets Ther Original Research BACKGROUND: The association of cancer stem cells with epithelial–mesenchymal transition (EMT) is receiving attention. We found in our previous study that EMT existed from CD24− phenotype cells to their differentiated cells. It was shown that cyclin D1 functioned in sustaining self-renewal independent of CDK4/CDK6 activation, but its effect on the EMT mechanism in ovarian cancer stem cells is unclear. METHODS: The anchorage-independent spheroids from ovarian adenocarcinoma cell line 3AO were formed in a serum-free medium. CD24− and CD24+ cells were isolated by fluorescence-activated cell sorting. Cell morphology, viability, apoptosis, and migratory ability were observed. Stem-related molecule Bmi-1, Oct-4 and EMT-related marker E-cadherin, and vimentin expressions were analyzed. Cyclin D1 expression in CD24− phenotype enriched spheroids was knocked down with small interfering RNA, and its effects on cell proliferation, apoptosis, migration ability, and EMT-related phenotype after transfection were observed. RESULTS: In our study, CD24− cells presented stronger proliferative, anti-apoptosis capacity, and migratory ability, than CD24+ cells or parental cells. CD24− cells grew with a scattered spindle-shape within 3 days of culture and transformed into a cobblestone-like shape, identical to CD24+ cells or parental cells at 7 days of culture. CD24− cells or spheroids highly expressed cyclin D1, Bmi-1, and vimentin, and seldom expressed E-cadherin, while CD24+ or parental cells showed the opposite expression. Furthermore, cyclin D1-targeted small interfering RNA resulted in decreased vimentin expression in spheroids. Transfected cells also exhibited an obvious decrease in cell viability and migration, but an increase in cell apoptosis. CONCLUSION: Cancer stem cell-like cells possess mesenchymal characteristics and EMT ability, and cyclin D1 involves in EMT mechanism, suggesting that EMT of cancer stem cell-like cells may play a key role in invasion and metastasis of ovarian cancer. Dove Medical Press 2013-06-20 /pmc/articles/PMC3699300/ /pubmed/23836980 http://dx.doi.org/10.2147/OTT.S44177 Text en © 2013 Jiao et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Jiao, Jie Huang, Lu Ye, Feng Shi, MinFeng Cheng, XiaoDong Wang, XinYu Hu, DongXiao Xie, Xing Lu, WeiGuo Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title | Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title_full | Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title_fullStr | Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title_full_unstemmed | Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title_short | Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
title_sort | cyclin d1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699300/ https://www.ncbi.nlm.nih.gov/pubmed/23836980 http://dx.doi.org/10.2147/OTT.S44177 |
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