Molecular Cancer | |
Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: Significance in claudin-low breast cancer cells | |
Research | |
Dilek Colak1  Olfat Al-Harazi1  Asma Tulbah2  Taher Al-Tweigeri3  Abdullah Alsuliman4  Hanaa Fitwi4  Monther Al-Alwan5  Hazem Ghebeh5  | |
[1] Department of Biostatistics, Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;Stem Cell & Tissue Re-engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;Stem Cell & Tissue Re-engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia; | |
关键词: CD274; Epithelial to Mesenchymal Transition; Claudin-low; PI3K; TGF-β1; Breast Cancer; | |
DOI : 10.1186/s12943-015-0421-2 | |
received in 2015-01-20, accepted in 2015-07-27, 发布年份 2015 | |
来源: Springer | |
【 摘 要 】
BackgroundThe T-cell inhibitory molecule PD-L1 (B7-H1, CD274) is expressed on tumor cells of a subset of breast cancer patients. However, the mechanism that regulates PD-L1 expression in this group of patients is still not well-identified.MethodsWe have used loss and gain of function gene manipulation approach, multi-parametric flow cytometry, large scale gene expression dataset analysis and immunohistochemistry of breast cancer tissue sections.ResultsInduction of epithelial to mesenchymal transition (EMT) in human mammary epithelial cells upregulated PD-L1 expression, which was dependent mainly on the activation of the PI3K/AKT pathway. Interestingly, gene expression signatures available from large cohort of breast tumors showed a significant correlation between EMT score and the PD-L1 mRNA level (p < 0.001). Strikingly, very strong association (p < 0.0001) was found between PD-L1 expression and claudin-low subset of breast cancer, which is known to have high EMT score. On the protein level, significant correlation was found between PD-L1 expression and standard markers of EMT (p = 0.005) in 67 breast cancer patients. Importantly, specific downregulation of PD-L1 in claudin-low breast cancer cells showed signs of EMT reversal as manifested by CD44 and Vimentin downregulation and CD24 upregulation.ConclusionsWe have demonstrated a bidirectional effect between EMT status and PD-L1 expression especially in claudin-low subtype of breast cancer cells. Our findings highlights the potential dual benefit of anti-PD-L1 particularly in this subset of breast cancer patients that will likely benefit more from anti-PD-L1 targeted therapy as well as in monitoring biological changes upon treatment.
【 授权许可】
CC BY
© Alsuliman et al. 2015
【 预 览 】
Files | Size | Format | View |
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RO202311103640131ZK.pdf | 2994KB | download | |
MediaObjects/42004_2023_1031_MOESM1_ESM.pdf | 4101KB | download |
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