In a new study published in Nature Communications, researchers at Karolinska Institutet and Queen Mary University of London have investigated how the physical structure of fat tissue helps ovarian cancer cells invade the body, offering potential new treatment strategies.
Ovarian cancer is known for its aggressive spread, often targeting fatty tissues in the abdomen. Now, a study published in Nature Communications by researchers at Karolinska Institutet and Queen Mary University of London reveals that it's not just chemical signals that guide this invasion-fat tissue's physical properties play a crucial role.
The research team discovered that ovarian cancer cells exploit the soft, crowded structure of visceral fat to move quickly and efficiently. Unlike previous studies that focused on biochemical cues, this research highlights how the large size and deformability of fat cells create "migration highways" for cancer cells. These pathways enable cancer cells to navigate through tight spaces without damaging their nuclei-a crucial factor in their survival and spread.
"Our study reveals how ovarian cancer cells exploit the unique physical properties of fat tissue to spread aggressively. Two key factors for creating 'migration highways' were cancer cell-induced adipocyte deformations and large adipocyte size, which both also correlated with aggressive tumours in patients. Developing and using innovative fat-mimicking models allowed us to untangle these physical drivers of metastasis, opening new avenues to target cancer's spread at its mechanical roots," says first author of the study and research specialist Jordi Gonzalez Molina at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet and at Queen Mary University of London
The study was conducted using advanced bioengineered models that replicate the structure of fat tissue, alongside patient-derived samples. This approach enabled researchers to isolate and study how specific features-such as fat cell size and tissue mechanics-impact cancer cell movement.
"Our newly engineered fat-mimicking platform opens doors to study other fat-linked cancers such as leukaemia, breast cancer, and gastric cancer. Ultimately, this work shifts the paradigm from solely targeting cancer cells to also manipulating their physical surroundings, a strategy that could transform how we combat metastasis in tumours known to involve fat", says Professor Kaisa Lehti , researcher at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet and Norwegian University of Science and Technology.
Next, the research team plans to investigate how other cell types, such as fibroblasts and immune cells, interact with cancer cells during fat tissue invasion. They also aim to explore how cancer cells trigger a fibrotic transformation in fat tissue, a process linked to therapy resistance.
Collaboration
The study is a collaboration between Professor Kaisa Lehti group at Karolinska Institutet and other teams at KI, as well as Professor Julien Gautrot's team at Queen Mary University of London, UK. A big thank you to the teams of Associate Professor Sahar Salehi and Assistant Professor Twana Alkasalias at KBH, who made the completion of this study possible.
Publication
Gonzalez-Molina, J., Nabili, P., Marciano, D. et al.
Nat Commun 16, 8541 (2025), doi: 10.1038/s41467-025-62296-7
