Sulfated Hyaluronan Drives Cell Adaptation and Matrix Composition in Advanced 3D Breast Cancer Cell Models.

Christos Koutsakis, Katerina Mineschou, Konstantinos Spanopoulos, Sylvia Mangani, Marco Franchi, Evgenia Karousou, Zoi Piperigkou, Nikos K Karamanos

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In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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5 · Who and what money

Authors and funding

8 authors.

Christos KoutsakisBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0000-0001-8705-7867

Katerina MineschouBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0009-0003-1055-8489

Konstantinos SpanopoulosBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0009-0007-0718-3726

Sylvia ManganiBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0009-0002-2013-7189

Marco FranchiDepartment for Life Quality Studies, University of Bologna, 47921 Rimini, Italy.ORCID 0000-0003-4133-3031

Evgenia KarousouDipartimento di Medicina e Chirurgia, Universitá Degli Studi Dell'Insubria, 21110 Varese, Italy.ORCID 0000-0002-2160-5290

Zoi PiperigkouBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0000-0002-0472-5389

Nikos K KaramanosBiochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece.ORCID 0000-0003-3618-0288

Funding

European Social Fund-ESF "Human Resources Development, Education and Lifelong Learning" in the context of the Act "En-hancing Human Resources Research Potential by undertaking a Doctoral Research" Sub-action 2: IKY Scholarship Programme for PhD candidatesEuropean Union Grant agreement ID: 101130985 "CARES-Human ECM-based platform for anti-cancer drug testing"

6 · The paper itself

Abstract

Hyaluronan (HA), a major extracellular matrix (ECM) glycosaminoglycan, plays a key role in breast cancer progression. Although native HA lacks sulfate groups, chemically modified sulfated hyaluronan (sHA) has demonstrated promising antitumor activity. Previous work from our group showed that sHA alters cellular functions and modulates ECM-related gene expression in triple-negative breast cancer (TNBC) cells. The aim of this study was to investigate the effects of low-molecular-weight HA (50 kDa) and its sulfated derivative of the same molecular weight, sHA, in MDA-MB-231 and MCF-7 breast cancer cells using advanced 3D cell culture models. Gene expression analyses focused on ECM components, including HA receptors and matrix metalloproteinases (MMPs) that were evaluated. The 3D cell morphology was examined using scanning electron microscopy (SEM). Spheroid growth and expression profiles linked to ECM remodeling and invasiveness were also assessed. Notably, sHA significantly inhibited 3D spheroid growth, reduced cell spreading in a cell line-dependent manner and influenced the expression of genes correlated with ECM remodeling and HA synthesis. These findings emphasize the importance of 3D models for studying ECM-driven breast cancer progression, further supporting sHA as a potential therapeutic modulator.

Indexed as

Adaptation, PhysiologicalBreast NeoplasmsExtracellular MatrixHyaluronic AcidModels, BiologicalSulfatesCell Culture Techniques, Three DimensionalCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansHyaluronan ReceptorsMCF-7 CellsMDA-MB-231 CellsSpheroids, CellularHyaluronan ReceptorsHyaluronic AcidSulfates3D cell platformsbreast cancerextracellular matrixhyaluronanspheroidssulfated hyaluronan

Identifiers

PMID42782787

DOI10.3390/cells15181687

PMCPMC13605643

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