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  3. Biomimetic organo-hydrogels reveal the adipose tissue local mechanical anisotropy regulates ovarian cancer invasion

Biomimetic organo-hydrogels reveal the adipose tissue local mechanical anisotropy regulates ovarian cancer invasion

  • Nat Commun. 2025 Sep 29;16(1):8541. doi: 10.1038/s41467-025-62296-7.
Jordi Gonzalez-Molina 1 2,  Parisa Nabili 3 4,  Daniele Marciano 5,  Sara Abdelnabi 3,  Okan Gultekin 3 4,  Mohammed Fatih Rasul 4 6,  Yikun Zhang 5,  Clémence Nadal 5,  Alexandra Chrysanthou 5,  Twana Alkasalias 4 7,  Sahar Salehi 4 8,  Frances Balkwill 9,  Kaisa Lehti 3 10,  Julien E Gautrot 11
Affiliations

Affiliations

  • 1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, Solna, Sweden. jordigonzalezmolina@gmail.com.
  • 2 School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, United Kingdom. jordigonzalezmolina@gmail.com.
  • 3 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, Solna, Sweden.
  • 4 Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Solnavägen, Solna, Sweden.
  • 5 School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, United Kingdom.
  • 6 Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Tishk International University, Erbil, Iraq.
  • 7 General Directorate of Scientific Research Centre, Salahaddin University-Erbil, Erbil, Iraq.
  • 8 Department of Pelvic Cancer, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
  • 9 Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, EC1M6BQ, London, UK.
  • 10 Department of Biomedical Laboratory Science, Norwegian University of Science and Technology - NTNU, Erling Skjalgssons gate 1, Trondheim, 7491, Norway.
  • 11 School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, United Kingdom. j.gautrot@qmul.ac.uk.
PMID: 41022685 DOI: 10.1038/s41467-025-62296-7
Abstract

High-grade serous ovarian Cancer, the most common and aggressive ovarian Cancer subtype, frequently metastasises to visceral adipose tissues. In these tissues, the extracellular matrix through which ovarian Cancer cells migrate is constrained by the presence and preponderance of adipocytes. How cells migrate in this unique environment is not known, yet critical to understanding metastatic progression. To study these processes, we developed biomimetic organo-hydrogels that recreate structural, mechanical, and biochemical properties of human adipose tissues. We show that ovarian Cancer cells present invasive tropism towards organo-hydrogels, replicating the behaviour observed in native adipose tissues. This migration is facilitated by the mechanical anisotropy and microstructure of organo-hydrogels and adipose tissues, allowing the formation of migratory tracks. These results highlight the contribution of adipocytes to tissue biophysical features as a key regulatory factor of ovarian Cancer cell migration and demonstrate that organo-hydrogels are particularly relevant tools to develop in vitro models of complex tissue architectures with high cellularity.

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