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.
This project was funded by a Swiss National Science Foundation Sinergia 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).
The most common types of ovarian and peritoneal cancers are diagnosed in a majority of 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 the Sinergia project, scientists from the AMI BioNanomaterials group and Prof. Heinzelmann’s team in 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 taking into account 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.
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.
Other publications from the project:
Jacob F, Marchetti RL, Kind AB, Russell K, Schoetzau A, Heinzelmann-Schwarz VA. High-grade serous peritoneal cancer follows a high stromal response signature and shows worse outcome than ovarian cancer. Mol Oncol 2021, 15(1):91-103. https://doi.org/10.1002/1878-0261.12811
Huang YL, Liang CY, Ritz D, Coelho R, Septiadi D, Estermann M, Cumin C, Rimmer N, Schötzau A, Núñez López M, Fedier A, Konantz M, Vlajnic T, Calabrese D, Lengerke C, David L, Rothen-Rutishauser B, Jacob F, Heinzelmann-Schwarz V. Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis. Elife 2020, 9:e59442. https://doi.org/10.7554/eLife.59442
Estermann M, Huang YL, Septiadi D, Ritz D, Liang CY, Jacob F, Drasler B, Petri-Fink A, Heinzelmann-Schwarz V, Rothen-Rutishauser B. Patient-derived and artificial ascites have minor effects on MeT-5A mesothelial cells and do not facilitate ovarian cancer cell adhesion. PLoS One 2020, 15(12):e0241500. https://doi.org/10.1371/journal.pone.0241500