Thieno[2,3- b]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s+ Breast Cancer Cells

噻吩并[2,3- b]吡啶衍生物靶向上皮、间质和混合 CD15s+ 乳腺癌细胞

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作者:Sandra Marijan, Angela Mastelić, Anita Markotić, Nikolina Režić-Mužinić, Nikolina Vučenović, David Barker, Lisa I Pilkington, Jóhannes Reynisson, Vedrana Čikeš Čulić

Abstract

The adhesion of cancer cells to vascular endothelium is a critical process in hematogenous metastasis and might be similar to the recruitment of leukocytes at the site of inflammation. It is mediated by E-selectin and its ligands, of which the most stereospecific is a glycoconjugate sialyl Lewis x (CD15s), which may be expressed as an oligosaccharide branch of the CD44 glycoprotein, as well as a self-contained glycosphingolipid. It is also known that increased sialylation of glycoconjugates is a feature of malignant cells. The aim of the study was to analyse the effect of a novel thieno[2,3-b]pyridine, compound 1, in MDA-MB-231 triple-negative breast cancer cells (TNBCs) upon CD15s and CD44 expression in different cell subpopulations using flow cytometry. CD15s expression was compared between mesenchymal-like cancer stem cells (CSC, CD44+CD24-), epithelial cells without CD44 (CD44-CD24+ and CD44-CD24-), and CD44+CD24+ cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s+CSC and CD15s-CSC was determined. Compound 1 significantly decreased the percentage of CD15s+CSC, CD15s+CD44+CD24+, and CD15s+CD44- subpopulations, as well as the expression of CD15s in CD44+CD24+ and CD44- cells, and therefore shows potential as a treatment for TNBC.

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