Name: Maria-Georgia Drosinou
Title: Sulfated hyaluronan modulates extracellular matrix composition and miRNA expression in 3D breast cancer spheroids
Date: 5 June 2026
Time: 10:00 am
Zoom link: https://upatras-gr.zoom.us/j/92702932162?pwd=oo2u933CgpbJ8SdUGVXkhyXLuLRGfj.1
Abstract
Cancer remains one of the most common diseases worldwide, as incidence rates increase steadily. Breast cancer is a biologically heterogeneous disease due to the existence of several molecular subtypes and varying clinical behavior. Extracellular matrix (ECM) is a three-dimensional (3D) macromolecular network, that not only provides structural support to cells, but also plays a critical role in regulating cell functional properties under both physiological and pathological conditions. Hyaluronan (HA), the only non-sulfated glycosaminoglycan (GAG), regulates breast cancer progression in a size-dependent manner. Our group has previously demonstrated that chemically sulfated hyaluronan (sHA) reduces the aggressive phenotype and ECM-related gene expression in triple-negative breast cancer cells, while inhibiting tumor growth in vivo. Within the tumor microenvironment (TME), ECM becomes notably stiffer due to the high accumulation of matrix components, which promotes tumor growth. Furthermore, microRNAs (miRNAs) are recognized as key epigenetic regulators and constituents of the TME, influencing cellular functions, including proliferation, migration, invasion, metastasis, and resistance to chemotherapy. MiRNAs are endogenous, non-coding short RNA molecules that regulate gene expression through post-transcriptional mechanisms. Depending the functional roles of target-mRNA, they regulate the expression of crucial matrix effectors, while vice versa interactions within the TME influence miRNA expression. In this context, our research group has demonstrated the functional role of specific miRNAs in the regulation of matrix expression, signaling and breast cancer cell behavior. Despite the insights provided by traditional 2D cultures in cancer research, they inadequately model the structural and biochemical complexity of the TME. As a result, cancer research focuses on 3D culture models that better reproduce the dynamic cell–matrix interactions found in solid tumors. This MSc thesis aimed to evaluate the effects of 50 kDa fragments of non-sulfated HA and sHA on the expression of key matrix macromolecules, including matrix metalloproteinases, proteoglycans, and HA receptors, as well as specific miRNAs involved in breast cancer progression (e.g., miR-10b-5p, miR-200b-3p, let-7d-5p) enriched with bioinformatic analysis by Kaplan-Meier Plotter and RAIN association and interaction networks. In addition, we investigated the impact of sHA on spheroid growth and functional properties in 3D cultures of breast cancer cells with distinct estrogen receptor (ER) status. Our findings demonstrated that sHA exerts significant inhibitory effects on breast cancer progression in 3D models and distinct miRNA expression profiles depending on ER status. Collectively, these findings will contribute to new molecular insights on the role of sHA in matrix and miRNA regulation during breast cancer progression, potentially guiding the development of novel matrix-based therapeutic strategies targeting aggressive breast cancer subtypes.
Three-member Evaluation Comittee
Zoi Piperigkou
Assistant Professor, Department of Chemistry, Supervisor
Nikos K. Karamanos
Professor, Department of Chemistry
Demitrios Vynios
Professor, Department of Chemistry