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

• Main Authors: Sandra Marijan, Angela Mastelić, Anita Markotić, Nikolina Režić-Mužinić, Nikolina Vučenović, David Barker, Lisa I. Pilkington, Jóhannes Reynisson, Vedrana Čikeš Čulić
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Medicines
• Subjects: triple-negative breast cancer; thieno[2,3-<i>b</i>]pyridine; CD15s glycosphingolipid; CD15s glycoprotein; CD44; CD24
• Online Access: https://www.mdpi.com/2305-6320/8/7/32
• ISSN: 2305-6320

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-<i>b</i>]pyridine, compound <b>1</b>, 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 <b>1</b> 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.