Name: Aikaterini-Eleftheria Mineschou
Title: Elastin-Derived Peptides (EDPs) Orchestrate Cancer Cell Plasticity and Molecular Dynamics across 2D and 3D cell models
Supervisor: Nikos K. Karamanos, Professor
Date: 15 June 2026
Time: 11:00 am
Zoom link: https://upatras-gr.zoom.us/j/92702932162?pwd=oo2u933CgpbJ8SdUGVXkhyXLuLRGfj.1
ABSTRACT: BREAST CANCER IS ONE OF THE MOST COMMON AND HETEROGENEOUS MALIGNANCIES AFFECTING WOMEN WORLDWIDE AND REMAINS A LEADING CAUSE OF CANCER-RELATED MORTALITY. IN ADDITION TO GENETIC AND MOLECULAR ALTERATIONS WITHIN TUMOR CELLS, CANCER PROGRESSION IS STRONGLY INFLUENCED BY THE TUMOR MICROENVIRONMENT (TME), PARTICULARLY THE EXTRACELLULAR MATRIX (ECM). THE ECM AS A DYNAMIC THREE-DIMENSIONAL NETWORK COMPOSED OF STRUCTURAL AND SIGNALING MOLECULES, INCLUDING COLLAGENS, ELASTIN, FIBRONECTIN, PROTEOGLYCANS, AND GLYCOSAMINOGLYCANS, REGULATES ESSENTIAL CELLULAR PROCESSES SUCH AS PROLIFERATION, SURVIVAL, MIGRATION, AND DIFFERENTIATION. ALTERATIONS IN ECM COMPOSITION AND ORGANIZATION CONTRIBUTE SIGNIFICANTLY TO TUMOR GROWTH, INVASION, AND METASTASIS. AMONG ECM COMPONENTS, ELASTIN IS A HIGHLY STABLE PROTEIN RESPONSIBLE FOR MAINTAINING TISSUE ELASTICITY. DURING AGING AND PATHOLOGICAL CONDITIONS, ELASTIN UNDERGOES PROTEOLYTIC DEGRADATION, LEADING TO THE RELEASE OF BIOACTIVE ELASTIN-DERIVED PEPTIDES (EDPS).
THESE PEPTIDES HAVE BEEN SHOWN TO MODULATE MULTIPLE CELLULAR PROCESSES ASSOCIATED WITH CANCER PROGRESSION, INCLUDING MIGRATION, INVASION, AND METASTATIC DISSEMINATION. DESPITE EXTENSIVE RESEARCH USING CONVENTIONAL TWO-DIMENSIONAL (2D) CELL CULTURE SYSTEMS, SUCH MODELS FAIL TO FULLY REPRODUCE THE COMPLEXITY OF THE IN VIVO TUMOR ENVIRONMENT. IN CONTRAST, THREE-DIMENSIONAL (3D) SPHEROID CULTURES BETTER MIMIC CELL-CELL AND CELL-ECM INTERACTIONS, PROVIDING A MORE PHYSIOLOGICALLY RELEVANT PLATFORM FOR STUDYING TUMOR BEHAVIOR.
The present study investigated the effects of EDPs, using kappa-elastin (kE) as an experimental model, on breast cancer cells cultured under both 2D and 3D conditions. The highly invasive triple-negative breast cancer cell line MDA-MB-231 and its ERβ-suppressed counterpart were employed to evaluate the potential involvement of estrogen receptor β (ERβ) in mediating the cellular responses to kE. Functional assays were performed to assess spheroid formation, migration, dissemination, and invasive capacity following kE treatment. In parallel, molecular analyses were conducted to examine the expression of genes and proteins associated with extracellular matrix remodeling, epithelial-to-mesenchymal transition (EMT), and the elastin receptor complex (ERC). Overall, the results demonstrate that kE modulates breast cancer cell behavior in a manner dependent on both the cellular microenvironment and ERβ expression status. These findings provide further evidence for the role of elastin-derived peptides in breast cancer progression and highlight the importance of 3D culture models as more representative systems for investigating tumor biology and microenvironmental interactions.