TY  - JOUR
AB  - Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.
AU  - Valla, Sofía
AU  - Hassan, Nourhan
AU  - Luján Vitale, Daiana
AU  - Madanes, Daniela
AU  - Spinelli, Fiorella Mercedes
AU  - Teixeira, Felipe C. O. B.
AU  - Greve, Burkhard
AU  - Espinoza-Sánchez, Nancy Adriana
AU  - Cristina, Carolina
AU  - Alaniz, Laura
AU  - Götte, Martin
DA  - 2021-05-30
DO  - 10.17879/53009588754
KW  - syndecan-1
KW  - hyaluronic acid
KW  - breast cancer
KW  - stem cells
KW  - apoptosis
KW  - angiogenesis
LA  - eng
N1  - International Journal of Molecular Sciences 22 (2021) 11, 5874, 1-24
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2021-05-30
TI  - Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-52099545900
Y2  - 2024-11-22T06:55:38
ER  -