Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> 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 (...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Medicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6320/8/7/32 |
| _version_ | 1797529283806101504 |
|---|---|
| author | Sandra Marijan Angela Mastelić Anita Markotić Nikolina Režić-Mužinić Nikolina Vučenović David Barker Lisa I. Pilkington Jóhannes Reynisson Vedrana Čikeš Čulić |
| author_facet | Sandra Marijan Angela Mastelić Anita Markotić Nikolina Režić-Mužinić Nikolina Vučenović David Barker Lisa I. Pilkington Jóhannes Reynisson Vedrana Čikeš Čulić |
| author_sort | Sandra Marijan |
| collection | DOAJ |
| description | 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<sup>+</sup>CD24<sup>−</sup>), epithelial cells without CD44 (CD44<sup>−</sup>CD24<sup>+</sup> and CD44<sup>−</sup>CD24<sup>−</sup>), and CD44<sup>+</sup>CD24<sup>+</sup> cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s<sup>+</sup>CSC and CD15s<sup>−</sup>CSC was determined. Compound <b>1</b> significantly decreased the percentage of CD15s<sup>+</sup>CSC, CD15s<sup>+</sup>CD44<sup>+</sup>CD24<sup>+</sup>, and CD15s<sup>+</sup>CD44<sup>−</sup> subpopulations, as well as the expression of CD15s in CD44<sup>+</sup>CD24<sup>+</sup> and CD44<sup>−</sup> cells, and therefore shows potential as a treatment for TNBC. |
| first_indexed | 2024-03-10T10:11:35Z |
| format | Article |
| id | doaj.art-4f274cb2505b4b368950015e472466b4 |
| institution | Directory Open Access Journal |
| issn | 2305-6320 |
| language | English |
| last_indexed | 2024-03-10T10:11:35Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicines |
| spelling | doaj.art-4f274cb2505b4b368950015e472466b42023-11-22T01:06:21ZengMDPI AGMedicines2305-63202021-06-01873210.3390/medicines8070032Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer CellsSandra Marijan0Angela Mastelić1Anita Markotić2Nikolina Režić-Mužinić3Nikolina Vučenović4David Barker5Lisa I. Pilkington6Jóhannes Reynisson7Vedrana Čikeš Čulić8Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaDepartment of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaDepartment of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaDepartment of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaDepartment of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaSchool of Chemical Sciences, The University of Auckland, Auckland 1010, New ZealandSchool of Chemical Sciences, The University of Auckland, Auckland 1010, New ZealandSchool of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UKDepartment of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, CroatiaThe 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<sup>+</sup>CD24<sup>−</sup>), epithelial cells without CD44 (CD44<sup>−</sup>CD24<sup>+</sup> and CD44<sup>−</sup>CD24<sup>−</sup>), and CD44<sup>+</sup>CD24<sup>+</sup> cells that exhibit mesenchymal and epithelial features. In addition, expression of CD44 in CD15s<sup>+</sup>CSC and CD15s<sup>−</sup>CSC was determined. Compound <b>1</b> significantly decreased the percentage of CD15s<sup>+</sup>CSC, CD15s<sup>+</sup>CD44<sup>+</sup>CD24<sup>+</sup>, and CD15s<sup>+</sup>CD44<sup>−</sup> subpopulations, as well as the expression of CD15s in CD44<sup>+</sup>CD24<sup>+</sup> and CD44<sup>−</sup> cells, and therefore shows potential as a treatment for TNBC.https://www.mdpi.com/2305-6320/8/7/32triple-negative breast cancerthieno[2,3-<i>b</i>]pyridineCD15s glycosphingolipidCD15s glycoproteinCD44CD24 |
| spellingShingle | Sandra Marijan Angela Mastelić Anita Markotić Nikolina Režić-Mužinić Nikolina Vučenović David Barker Lisa I. Pilkington Jóhannes Reynisson Vedrana Čikeš Čulić Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells Medicines triple-negative breast cancer thieno[2,3-<i>b</i>]pyridine CD15s glycosphingolipid CD15s glycoprotein CD44 CD24 |
| title | Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells |
| title_full | Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells |
| title_fullStr | Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells |
| title_full_unstemmed | Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells |
| title_short | Thieno[2,3-<i>b</i>]Pyridine Derivative Targets Epithelial, Mesenchymal and Hybrid CD15s<sup>+</sup> Breast Cancer Cells |
| title_sort | thieno 2 3 i b i pyridine derivative targets epithelial mesenchymal and hybrid cd15s sup sup breast cancer cells |
| topic | triple-negative breast cancer thieno[2,3-<i>b</i>]pyridine CD15s glycosphingolipid CD15s glycoprotein CD44 CD24 |
| url | https://www.mdpi.com/2305-6320/8/7/32 |
| work_keys_str_mv | AT sandramarijan thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT angelamastelic thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT anitamarkotic thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT nikolinarezicmuzinic thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT nikolinavucenovic thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT davidbarker thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT lisaipilkington thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT johannesreynisson thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells AT vedranacikesculic thieno23ibipyridinederivativetargetsepithelialmesenchymalandhybridcd15ssupsupbreastcancercells |