Name: Nikolaos Koletsis
Title: Functional properties and differential expression of key matrix components in three dimensional breast cancer spheroids
Supervisor: Nikos Karamanos, Professor
Date: 02/06/2025
Time: 10.00 am
Zoom link: https://upatras-gr.zoom.us/j/96516568158?pwd=bbhcVOhnjiDkYcHAn8ZzQNxPCgnA5e.1
Tumor microenvironment dynamic interactions play critical roles in premetastatic niche, cancer cells invasion and metastatic potential. The three-dimensional (3D) extracellular matrices (ECMs) structural networks are capable of modulating cell functional properties. Traditional 2D cultures have offered valuable insights in cellular behavior, although lacking the ability of accurately representing the complex matrix microenvironment structure in vivo. Thus, developing in vitro cell models that could mimic the 3D morphological aspects of solid tumors in vivo, could improve our understanding on tumor growth and progression.
This study focuses on the development of three-dimensional cell culture models, particularly on breast cancer derived spheroids utilizing two breast cancer cell lines, shERβ MDA-MB-231 (derived from the highly aggressive MDA-MB-231 ERbeta-positive cell line) and Hs578T. Estrogen receptors (ERs) have pivotal roles in breast cancer growth and progression. Even though the contribution of ERα in the modulation of breast cancer cells' behavior is thoroughly studied, the biological functions of its isoform, ERβ, are less elucidated.
The aim of this study is to examine possible morphological alterations in the formation of the different cell line 3D-spheroids, accompanied by variations in the expression of ECM macromolecules implicated in cancer progression comparatively to the respective cell lines grown in 2D culture flasks in the presence and absence of matrix macromolecules.
To this end, total RNA was extracted, and 3D spheroid formation and behavior was evaluated as to examine the 3D-spheroids functional properties. The obtained data revealed significant variations in the expression of ECM macromolecules, mesenchymal markers, receptors, proteases in 3D cell models, as compared with respective 2D cell cultures. Ultimately, this study underscores the importance of focusing on 3D cultures, as these more innovative cell culture models offer deeper insights into breast cancer research.