Name: Marios Vetoulas
Title: Exploring Integrin-Matrix interactions in 2D and 3D ECM contexts in Breast Cancer Models
Supervisor: Nikos K. Karamanos, Professor
Date: 15/6/2026
Time: 10.00
Link: https://upatras-gr.zoom.us/j/92702932162?pwd=oo2u933CgpbJ8SdUGVXkhyXLuLRGfj.1
Abstract
Breast cancer progression is strongly shaped by interactions between tumor cells and the extracellular matrix (ECM). ECM composition, culture dimensionality and integrin-mediated matrix sensing regulate key processes such as adhesion, spheroid organization, dissemination and gene expression. In this study, Hs578T and shERβ MDA-MB-231 breast cancer cells were used to investigate how collagen type I, fibronectin, HA and sulfated HA (sHA, ~50 kDa) affect tumor cell behavior in 2D and 3D ECM contexts. Multicellular tumor spheroids were used to evaluatespheroid growth, matrix-dependent organization and dissemination under matrix-free, collagen type I-, fibronectin- and mixed collagen / fibronectin-containing conditions. In parallel, HA and sHA treatments were applied to assess their effects on spheroid behavior and ECM-dependent responses. Bioinformatic analyses supported the selection of collagen- and fibronectin-associated integrin subunits, which were further examined by real-time qPCR under 2D and 3D cell culture conditions.
The results showed that ECM composition strongly influenced spheroid organization and dissemination. Collagen type I promoted greater outward dissemination, whereas fibronectin-rich matrices were associated with more compact organization and reduced spreading. sHA altered spheroid growth dynamics and disrupted organized spheroid formation within ECM-rich environments, suggesting that it acts as a bioactive modulator of tumor cell–matrix interactions. Integrins’ expression analyses further revealed model-dependent remodeling, with shERβ MDA-MB-231 cells showing broader induction of adhesion-related integrins, while Hs578T cells displayed stronger dimensionality-driven downregulation of selected matrix-associated integrins together with consistent ITGB3 induction. Overall, these findings highlight the importance of integrin–ECM communication in breast cancer cell behavior and support further investigation of sulfated HA as an ECM-associated molecule with anti-cancer relevance in 3D breast cancer models.