Abstract:
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.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Jiao J,Huang L,Ye F,Shi M,Cheng X,Wang X,Hu D,Xie X,Lu Wdoi
10.2147/OTT.S44177subject
Has Abstractpub_date
2013-06-20 00:00:00pages
667-77issn
1178-6930pii
ott-6-667journal_volume
6pub_type
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
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