Biomimetic organo-hydrogels reveal the adipose tissue local mechanical anisotropy regulates ovarian cancer invasion
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.
Authors
- Sahar Salehi (ORCID: https://orcid.org/0000-0002-5426-2570)
- Sara Abdelnabi
- Twana Alkasalias (ORCID: https://orcid.org/0000-0003-4567-2364)
- Okan Gultekin (ORCID: https://orcid.org/0000-0003-0248-2384)
- Alexandra Chrysanthou (ORCID: https://orcid.org/0000-0003-0418-0590)
- Clémence Nadal (ORCID: https://orcid.org/0009-0004-0070-8284)
- Mohammed Fatih Rasul (ORCID: https://orcid.org/0000-0003-4742-230X)
- Jordi Gonzalez‐Molina (ORCID: https://orcid.org/0000-0003-4306-1498)
- Frances R. Balkwill (ORCID: https://orcid.org/0000-0002-5587-9759)
- Julien E. Gautrot (ORCID: https://orcid.org/0000-0002-1614-2578)
- Kaisa Lehti (ORCID: https://orcid.org/0000-0001-9110-8719)
- Yikun Zhang (ORCID: https://orcid.org/0000-0001-7259-2867)
- Parisa Nabili
- Daniele Marciano (ORCID: https://orcid.org/0000-0002-2996-6146)
Institutions
- Karolinska University Hospital (SE)
- Queen Mary University of London (GB)
- Norwegian University of Science and Technology (NO)
- Karolinska Institutet (SE)
- Salahaddin University-Erbil (IQ)
- Tishk International University (IQ)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41467-025-62296-7
- Citations
- 2
- Primary Topic
- Tissue Engineering and Regenerative Medicine
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- Japan Chemical Industry Association
- Cancerfonden
- Karolinska Institutet
- Novo Nordisk
- Stockholms Läns Landsting
- China Scholarship Council
- Svenska Läkaresällskapet
- Novo Nordisk Fonden
- Engineering and Physical Sciences Research Council