Skip to main content

ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1450407
This article is part of the Research Topic Editors’ Showcase 2024: Insights in Cancer Cell Biology View all articles

Cisplatin resistance alters ovarian cancer spheroid formation and impacts peritoneal invasion

Provisionally accepted
Lydia C Powell Lydia C Powell 1*Marcos Quintela Marcos Quintela 1David James David James 1Emenike Onyido Emenike Onyido 1David Howard David Howard 1Kadie Edwards Kadie Edwards 1Jenny Worthington Jenny Worthington 2Nicole Williams Nicole Williams 2Alexander Dulebo Alexander Dulebo 3Heiko Haschke Heiko Haschke 3Deyarina Gonzalez Deyarina Gonzalez 1R. Steven Conlan R. Steven Conlan 1Lewis Webb Francis Lewis Webb Francis 1*
  • 1 Swansea University Medical School, Swansea, United Kingdom
  • 2 AxisBio Discovery Services, Londonderry, United Kingdom
  • 3 Bruker Nano GmbH, Berlin, Berlin, Germany

The final, formatted version of the article will be published soon.

    Epithelial ovarian cancer (EOC) is an aggressive and lethal gynaecologic malignancy due to late diagnosis and acquired resistance to chemotherapeutic drugs, such as cisplatin. EOC metastasis commonly occurs through the extensive dissemination of multicellular aggregates, formed of cells originally shed from the primary ovarian tumour, within the peritoneal cavity.However, little is known about how cisplatin resistance (CR) alters the biophysical properties of EOC multicellular aggregates and how this impacts metastasis. In this interdisciplinary study, light and atomic force microscopy was used, alongside quantitative gene and protein expression analysis, to reveal distinct differences in the biophysical properties of CR spheroids, which correlated with altered protein expression of plasminogen activator inhibitor-1 (PAI-1) and Tenascin-C. CR SKOV3 spheroids (IC50: 25.5 µM) had a significantly greater area and perimeter and were less spherical, with a reduced Young's modulus, (p< 0.01) compared to parental (P) SKOV3 spheroids (IC50: 5.4 µM). Gene expression arrays revealed up-regulation of genes associated with cell adhesion, ECM and epithelial-to-mesenchymal transition (EMT) in CR spheroids, while immunofluorescence assays demonstrated increased protein expression of PAI-1 (p<0.05; implicated in cell adhesion) and reduced protein expression of Tenascin-C (p<0.01; implicated in elasticity) in CR spheroids compared to P spheroids. Furthermore, the CR spheroids demonstrated altered interactions with a surface that mimics the peritoneal liningsurface post mesothelial clearance (Matrigel). CR spheroids were significantly less adhesive with reduced disaggregation on Matrigel surfaces, compared to P spheroids (p<0.05), while CR cells were more invasive compared to P cells. The combined characterisation of the biophysical and biological roles of EOC multicellular aggregates in drug resistance and metastasis highlight key proteins which could be responsible for altered metastatic progression that may occur in patients that present with cisplatin resistance.

    Keywords: ovarian cancer, spheroids, Biophysics, invasion, Atomic Force Microscopy, Cisplatin

    Received: 17 Jun 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Powell, Quintela, James, Onyido, Howard, Edwards, Worthington, Williams, Dulebo, Haschke, Gonzalez, Conlan and Francis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lydia C Powell, Swansea University Medical School, Swansea, United Kingdom
    Lewis Webb Francis, Swansea University Medical School, Swansea, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.