{
  "abstract": "Background: Breast cancer progression is strongly influenced by tumor cell interactions with the extracellular matrix (ECM). Three-dimensional (3D) cell culture models provide more relevant systems for studying aspects of the tumor microenvironment (TME), including tumor architecture, matrix remodeling and cell-ECM communication. Collagen type I (Col I), fibronectin (FN) and hyaluronan (HA) are key ECM components involved in breast cancer progression. At the same time, integrins act as major matrix-sensing receptors that translate ECM cues into cellular responses. In this study, we investigated how defined ECM contexts regulate functional cell properties in shERβ MDA-MB-231 and Hs578T advanced 3D breast cancer cell models. Methods: Cells were cultured in 2D and 3D systems under matrix-free conditions or in Col I, FN, and mixed Col I/FN environments, in the presence or absence of HA or sulfated HA (sHA). Spheroid growth, matrix-dependent spheroid organization and dissemination were evaluated. In parallel, selected collagen- and fibronectin-associated integrin subunits, together with HA-related molecules including HAS2, CD44, and RHAMM, were analyzed to assess receptor-mediated matrix- and HA-associated responses. Results: Matrix substrates strongly influenced breast cancer spheroid behavior. Col I promoted outward dissemination, whereas FN-containing environments favored compact organization and restricted spreading. HA supported spheroid-like organization in a matrix-dependent manner, whereas sHA disrupted organized spheroid assembly in ECM-rich conditions, resulting in looser structures or smaller cell colonies, depending on the matrix context. Gene expression analysis revealed model-dependent remodeling of matrix- and HA-associated programs, with broader adhesion-related responses in shERβ MDA-MB-231 cells and stronger dimensionality-driven regulation in Hs578T cells. Conclusions: Overall, these findings demonstrate that defined ECM contexts actively regulate breast cancer spheroid behavior and matrix-associated receptor programs. Col I, FN and mixed Col I/FN environments generated distinct 3D phenotypes, affecting spheroid growth, organization and dissemination, while HA/sHA further modified these matrix-dependent responses. This study supports sHA as a functional matrix molecule with anti-cancer relevance and highlights the value of 3D matrix-based models for investigating tumor–matrix communication in breast cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marios Vetoulas",
      "orcid": "0009-0004-5964-4692"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Drosinou"
    },
    {
      "affs": [
        0
      ],
      "name": "Nikoleta Alexiou",
      "orcid": "0009-0007-3499-4022"
    },
    {
      "affs": [
        0
      ],
      "name": "Angeliki Farmaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Zoi Piperigkou",
      "orcid": "0000-0002-0472-5389"
    },
    {
      "affs": [
        0
      ],
      "name": "Nikos K. Karamanos",
      "orcid": "0000-0003-3618-0288"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7e7e7msjpvnk9.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18203288",
  "fulltext_url": null,
  "id": "7e7e7msjpvnk9",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/20/3288",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Cellular Mechanics and Interactions"
    ]
  ],
  "openalex": "W7221505334",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7e7e7msjpvnk9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18203288",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/20/3288"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Cellular Mechanics and Interactions",
      "subfield": "cell-biology"
    }
  ],
  "title": "Defined Extracellular Matrix Contexts Rewire 3D Breast Cancer Cell Models: Effects of Sulfated Hyaluronan in the Expression of Matrix Effector and Matrix-Based Cell Functional Properties",
  "title_text": "Defined Extracellular Matrix Contexts Rewire 3D Breast Cancer Cell Models: Effects of Sulfated Hyaluronan in the Expression of Matrix Effector and Matrix-Based Cell Functional Properties",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/7e7e7msjpvnk9",
  "venue": "Cancers",
  "versions": []
}