Understanding ovarian cancer

Researchers from the Adolphe Merkle Institute’s BioNanomaterials group and other institutions have developed a multicellular 3D human omentum model to study the formation of ovarian and peritoneal cancer. This is aimed at providing a better understanding of how these cancers spread. 

The most common types of ovarian and peritoneal cancers are diagnosed in most cases at an advanced stage, with the likelihood of surviving more than five years just around 20 per cent. When these different cancers metastasize, the majority present a preference for the greater omentum, a visceral peritoneal fold within the abdominal cavity. Understanding this spreading process could provide vital insights into the cancers.

The overall aim of this collaboration was to understand the role of the omentum in the context of this complex disease thereby studying its architecture in-situ, generate a human omentum cell atlas, identify mechanisms in cancer cells promoting spread towards the omentum, generate a molecular information at the single cell level and to design, based on the in-situ information, a relevant 3D human model investigating ovarian cancer cell.

Researchers have previously considered experimental tissue models with limited combinations of the different omentum cell types. These have however been unable to convey the complexity of the interactions of those cells, and the effects of these interactions on metastatic behavior. As part of a Sinergia project funded by the Swiss National Science Foundation, scientists from the AMI BioNanomaterials group and colleagues at the University of Basel chose to tackle the problem by developing a bioprinted 3D multi-cellular human omentum tissue model, consisting of mesothelial cells, fibroblasts, macrophages, adipocytes, and endothelial cells. This model parallels more closely with the local tissue heterogeneity of human omentum in vivo by considering the spatial arrangement of the different cell types. By exposing it to ovarian cancer cells, it provides a more accurate representation of the tumor microenvironment.

“With our most recent publication were able to show that viable multi-cellular ovarian cancer aggregates exhibited invasive behavior similar to metastasis when applied to our 3D tissue model,” adds the AMI BioNanomaterials co-chair, Prof. Barbara Rothen-Rutishauser. “Our data suggest that our model can be used in future studies to investigate ovarian cancer cell invasion, metastatic behavior, and interaction between patient-derived cancer and omental cells, opening a path to more personalized treatments for ovarian cancer.”

The researchers believe that their project has been a success, as it opens the door to future use of the 3D tissue model. Knowledge generated about the omentum tumor microenvironment using single-cell RNA sequencing during the Sinergia project will serve as the starting point to address specific research questions with the 3D model.

This project was funded by a grant (“The underestimated role of the human omentum in metastatic spread”), worth a total of almost CHF 2 million over four years. This grant promoted the interdisciplinary collaboration of four research groups, in this case the teams of Prof. Viola Heinzelmann (Department of Biomedicine at the University Hospital Basel and University of Basel), Prof. Uwe Pieles (University of Applied Sciences School of Sciences (FHNW)), Prof. Ivan Martin (Biomedicine, University of Basel) and Prof. Barbara Rothen-Rutishauser (Adolphe Merkle Institute, University of Fribourg).

“This kind of collaboration is extremely important, since it helps us develop a comprehensive and more efficient approach to problem-solving, something we would not necessarily achieve alone,” adds Rothen-Rutishauser. “It also facilitates the transfer of knowledge and skills between institutions, enhancing the overall scientific capacity.”

Reference: Estermann, M.; Coelho, R.; Jacob, F.; Huang, Y.-L.; Liang, C.-Y.; Faia-Torres, A. B.; Septiadi, D.; Drasler, B.; Karakocak, B. B.; Dijkhoff, I. M.; Petri-Fink, A.; Heinzelmann-Schwarz, V.; Rothen-Rutishauser, B. A 3D Multi-Cellular Tissue Model of the Human Omentum to Study the Formation of Ovarian Cancer Metastasis. Biomaterials 2023, 294, 121996. https://doi.org/10.1016/j.biomaterials.2023.121996.