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

Jordi Gonzalez-Molina (), Parisa Nabili, Daniele Marciano, Sara Abdelnabi, Okan Gultekin, Mohammed Fatih Rasul, Yikun Zhang, Clémence Nadal, Alexandra Chrysanthou, Twana Alkasalias, Sahar Salehi, Frances Balkwill, Kaisa Lehti and Julien E. Gautrot ()
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Jordi Gonzalez-Molina: Solnavägen 9
Parisa Nabili: Solnavägen 9
Daniele Marciano: Mile End Road
Sara Abdelnabi: Solnavägen 9
Okan Gultekin: Solnavägen 9
Mohammed Fatih Rasul: Solnavägen
Yikun Zhang: Mile End Road
Clémence Nadal: Mile End Road
Alexandra Chrysanthou: Mile End Road
Twana Alkasalias: Solnavägen
Sahar Salehi: Solnavägen
Frances Balkwill: EC1M6BQ
Kaisa Lehti: Solnavägen 9
Julien E. Gautrot: Mile End Road

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62296-7

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