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

Autor: Marijan S; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Mastelić A; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Markotić A; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Režić-Mužinić N; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Vučenović N; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Barker D; School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand.; MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington 6140, New Zealand., Pilkington LI; School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand., Reynisson J; School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UK., Čulić VČ; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia.
Jazyk: angličtina
Zdroj: Medicines (Basel, Switzerland) [Medicines (Basel)] 2021 Jun 22; Vol. 8 (7). Date of Electronic Publication: 2021 Jun 22.
DOI: 10.3390/medicines8070032
Abstrakt: 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.
Databáze: MEDLINE