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

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.