Abstract:
BACKGROUND:We have previously shown that galactosylceramide (GalCer) affects the tumourigenic and metastatic properties of breast cancer cells by acting as an anti-apoptotic molecule. Since GalCer is a precursor molecule in the synthesis of sulfatides, the present study was aimed to define the role of sulfatides in apoptosis and breast cancer progression. METHODS:Expression of GAL3ST1 in breast cancer cell lines and breast cancer tissue specimens was analysed using real-time PCR, western blotting and immunohistochemistry analysis. The amount of sulfatide, GalCer and ceramide was analysed by thin-layer chromatography binding assay and by the modified hydrophilic interaction liquid chromatography coupled with electrospray mass spectrometry methodology. The tumourigenicity of cancer cells was analysed by an in-vivo tumour growth assay. Apoptotic cells were detected based on caspase-3 activation and the TUNEL assay. The interaction of breast cancer cells with P-selectin or E-selectin was analysed using the flow adhesion assay. The ability of sulfatide-expressing cells to activate and aggregate platelets was studied using the flow-cytometry-based aggregation assay. RESULTS:Using two models of breast cancer, T47D cells with blocked synthesis of sulfatide and MDA-MB-231 cells with neosynthesis of this glycosphingolipid, we showed that high sulfatide levels resulted in increased sensitivity of cancer cells to apoptosis induced by hypoxia and doxorubicin in vitro, and decreased their tumourigenicity after transplantation into athymic nu/nu mice. Accordingly, a clinical study on GAL3ST1 expression in invasive ductal carcinoma revealed that its elevated level is associated with better prognosis. Using MDA-MB-231 cells with neosynthesis of sulfatide we also showed that sulfatide is responsible for adhesion of breast cancer cells to P-selectin-expressing cells, including platelets. Sulfatide also acted as an activating molecule, increasing the expression of P-selectin. CONCLUSIONS:This study demonstrates that increased synthesis of sulfatide sensitises cancer cells to microenvironmental stress factors such as hypoxia and anticancer drugs such as doxorubicin. However, sulfatide is probably not directly involved in apoptotic cascades, because its increased synthesis by GAL3ST1 decreased the amounts of its precursor, GalCer, a known anti-apoptotic molecule. On the other hand, our data support the view that sulfatides are malignancy-related adhesive molecules involved in activating and binding P-selectin-expressing platelets to breast cancer cells.
journal_name
Breast Cancer Resjournal_title
Breast cancer research : BCRauthors
Suchanski J,Grzegrzolka J,Owczarek T,Pasikowski P,Piotrowska A,Kocbach B,Nowak A,Dziegiel P,Wojnar A,Ugorski Mdoi
10.1186/s13058-018-1058-zsubject
Has Abstractpub_date
2018-11-06 00:00:00pages
133issue
1eissn
1465-5411issn
1465-542Xpii
10.1186/s13058-018-1058-zjournal_volume
20pub_type
杂志文章abstract:INTRODUCTION:The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that de...
journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
doi:10.1186/bcr956
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression th...
journal_title:Breast cancer research : BCR
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journal_title:Breast cancer research : BCR
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更新日期:2013-03-12 00:00:00
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doi:10.1186/s13058-019-1232-y
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
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abstract:BACKGROUND:Although recent models suggest that the detection of Circulating Tumor Cells (CTC) in epithelial-to-mesenchymal transition (EM CTC) might be related to disease progression in metastatic breast cancer (MBC) patients, current detection methods are not efficient in identifying this subpopulation of cells. Furth...
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
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journal_title:Breast cancer research : BCR
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:10.1186/bcr1740
更新日期:2007-01-01 00:00:00
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更新日期:2002-01-01 00:00:00
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更新日期:2014-03-14 00:00:00
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pub_type: 杂志文章,多中心研究
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pub_type: 评论,社论
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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更新日期:2009-01-01 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,meta分析
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更新日期:2007-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章
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更新日期:2019-05-22 00:00:00
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journal_title:Breast cancer research : BCR
pub_type: 杂志文章,多中心研究
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更新日期:2010-01-01 00:00:00