Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim of the present...
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MDPI AG
2021-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/12/1916 |
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| author | Christos Koutsakis Anastasia-Gerasimoula Tavianatou Dimitris Kokoretsis Georgios Baroutas Nikos K. Karamanos |
| author_facet | Christos Koutsakis Anastasia-Gerasimoula Tavianatou Dimitris Kokoretsis Georgios Baroutas Nikos K. Karamanos |
| author_sort | Christos Koutsakis |
| collection | DOAJ |
| description | Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim of the present study was to evaluate the effects sHA fragments have on breast cancer cells with different estrogen receptor (ER) status. To this end, ERα-positive MCF-7, and ERβ-positive MDA-MB-231 cells were treated with non-sulfated HA or sHA fragments of 50 kDa. The functional properties of the breast cancer cells and the expression of key matrix effectors were investigated. According to the results, sHA attenuates cell proliferation, migration, and invasion, while increasing adhesion on collagen type I. Furthermore, sHA modulates the expression of epithelial-to-mesenchymal transition (EMT) markers, such as <span style="font-variant: small-caps;">e</span>-cadherin and snail2/slug. Additionally, sHA downregulates matrix remodeling enzymes such as the matrix metalloproteinases MT1-MMP, MMP2, and MMP9. Notably, sHA exhibits a stronger effect on the breast cancer cell properties compared to the non-sulfated counterpart, dependent also on the type of cancer cell type. Consequently, a deeper understanding of the mechanism by which sHA facilitate these processes could contribute to the development of novel therapeutic strategies. |
| first_indexed | 2024-03-10T04:32:36Z |
| format | Article |
| id | doaj.art-3ae17e5bdf1b4a6784c7914ce795af14 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T04:32:36Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-3ae17e5bdf1b4a6784c7914ce795af142023-11-23T04:01:13ZengMDPI AGBiomolecules2218-273X2021-12-011112191610.3390/biom11121916Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor StatusChristos Koutsakis0Anastasia-Gerasimoula Tavianatou1Dimitris Kokoretsis2Georgios Baroutas3Nikos K. Karamanos4Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, GreeceBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, GreeceBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, GreeceBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, GreeceBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, GreeceHyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim of the present study was to evaluate the effects sHA fragments have on breast cancer cells with different estrogen receptor (ER) status. To this end, ERα-positive MCF-7, and ERβ-positive MDA-MB-231 cells were treated with non-sulfated HA or sHA fragments of 50 kDa. The functional properties of the breast cancer cells and the expression of key matrix effectors were investigated. According to the results, sHA attenuates cell proliferation, migration, and invasion, while increasing adhesion on collagen type I. Furthermore, sHA modulates the expression of epithelial-to-mesenchymal transition (EMT) markers, such as <span style="font-variant: small-caps;">e</span>-cadherin and snail2/slug. Additionally, sHA downregulates matrix remodeling enzymes such as the matrix metalloproteinases MT1-MMP, MMP2, and MMP9. Notably, sHA exhibits a stronger effect on the breast cancer cell properties compared to the non-sulfated counterpart, dependent also on the type of cancer cell type. Consequently, a deeper understanding of the mechanism by which sHA facilitate these processes could contribute to the development of novel therapeutic strategies.https://www.mdpi.com/2218-273X/11/12/1916sulfated hyaluronanextracellular matrixbreast cancerestrogen receptorsepithelial-to-mesenchymal transitionmatrix metalloproteinases |
| spellingShingle | Christos Koutsakis Anastasia-Gerasimoula Tavianatou Dimitris Kokoretsis Georgios Baroutas Nikos K. Karamanos Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status Biomolecules sulfated hyaluronan extracellular matrix breast cancer estrogen receptors epithelial-to-mesenchymal transition matrix metalloproteinases |
| title | Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status |
| title_full | Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status |
| title_fullStr | Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status |
| title_full_unstemmed | Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status |
| title_short | Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status |
| title_sort | sulfated hyaluronan modulates the functional properties and matrix effectors expression of breast cancer cells with different estrogen receptor status |
| topic | sulfated hyaluronan extracellular matrix breast cancer estrogen receptors epithelial-to-mesenchymal transition matrix metalloproteinases |
| url | https://www.mdpi.com/2218-273X/11/12/1916 |
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