A Better Model for Understanding Ovarian Cancer

Unfortunately ovarian and peritoneal cancers are often diagnosed at a stage that is already quite advanced. This greatly reduces the chances of survival for patients battling such cancers. To tackle this problem, a research team at the Adolphe Merkle Institute, in association with three other Swiss institutions, has developed a 3D model of tissue that makes it possible to better understand the processes by which the disease spreads.

Generally it is at a late stage that doctors are able to diagnose the most common types of cancer of the ovaries and peritoneum (the membrane lining the inside wall of the abdomen, covering the uterus and extending over the bladder and rectum). Consequently, the five-year survival rate rarely exceeds 20%. Medical researchers are already aware that when these cancers metastasize, the cancerous cells frequently migrate towards the epiploon, better known as the greater omentum, a large fold in the peritoneum. To understand the how and why of this propagation will quite likely provide valuable information in the fight against the disease.

A 3D model
Working with researchers from other Swiss institutions, in particular the University of Basel’s Prof. Viola Heinzelmann, the scientists of the BioNanomaterials Group at the Adolphe Merkle Institute have developed a three-dimensional multicellular model of the greater omentum in humans. Their approach has led to three significant breakthroughs, making it possible to formulate a human cell atlas of the greater omentum; identify the mechanisms that encourage cancerous cells to migrate towards the greater omentum; and finally gather molecular information at the level of the individual cell. Thanks to this 3D model, the scientists now have a better understanding of the interactions between patients’ cancers and the cells of the greater omentum. «It’s absolutely essential if you want to develop more personalized therapies,» as Professor Barbara Rothen-Rutishauser of the Merkle Institute’s BioNanomaterials Group enthusiastically points out.

A scientific advance that is the result of a broad collaboration
In the past, scientists had tried to devise experimental models but these only yielded a confused image of the complexity that characterizes the interactions of cancerous cells and the greater omentum. On the other hand, working together made it possible to better comprehend the disease’s mechanisms by developing 3D bioprinted tissue of the famous greater omentum. The model is made up of a range of cells, i.e., mesothelial cells, fibroblasts, macrophages, adipocytes, and endothelial cells. The model therefore more closely reflects the variety of local in vivo tissue in humans’ greater omentum. «It brings more precision to considering the spatial layout of different cell types,» Professor Rothen-Rutishauser stresses. «Once it is exposed to ovarian cancer cells, it gives us a more precise picture of the tumor microenvironment.» This success paves the way for future uses of 3D modeling of tissue.

Manuela Estermann, Ricardo Coelho, Barbara Rothen-Rutishauser et al. A 3D multi-cellular tissue model of the human omentum to study the formation of ovarian cancer metastasis. In: Biomaterials, Volume 294, March 2023