ERC proof-of-concept funding for 'Design2Guide': New design strategy for experimental models of tumour tissues

The team's research addresses a clinical problem with an innovative approach. Pancreatic cancer is one of the deadliest cancers and only 10% of people diagnosed with the disease survive five years after diagnosis. In order to find better therapies, patient-specific models are being developed that mimic the biology of tumour tissue and interactions between different cell types. The aim of 'Design2Guide' is to create a controllable platform for experimental studies on human disease in the laboratory. The new platform will be used to find better treatments for the disease.

The poor prognosis for pancreatic cancer is partly due to the fact that the tumours are surrounded by fibrotic tissue and an extracellular collagen matrix. Matrix proteins regulate important cell functions. The fibrotic tissue and matrix of this disease cannot be replicated with available experimental models. Several studies, including two by Daniela Lössner's team (Advanced Healthcare Materials 2022 doi: 10.1002/adhm.202201907, Nature Communications 2021 doi: 10.1038/s41467-021-25921-9), have highlighted the key role of individual matrix components in controlling cell function and emphasise the need to develop hydrogel-based systems.

The problem:
The extracellular matrix of pancreatic tumours is very complex and consists of many fibrotic proteins, including collagens, proteoglycans, laminins and fibronectin. In tumour tissues, matrix remodelling stimulates the growth of cancer cells, which in turn interact with the matrix via integrins, an important class of cell surface and adhesion receptors (Figure 1A). Integrins facilitate cell-cell and cell-matrix interactions in the tumour environment and control signalling pathways that lead to disease progression and metastasis (Figure 1B). Integrins have therefore become an important subject of research into new therapies that are being tested in clinical trials. However, despite the important role of cell adhesion, a robust technical approach to mimic the specific adhesion profile of cancer cells and to study the disease-relevant integrin profile in experimental models is lacking.

The solution:
'Design2Guide' proposes a rational design strategy for a disease-relevant 3D cancer model based on two fundamental aspects: Firstly, a minimalistic synthetic matrix containing individual matrix components of tumour tissues in the form of polyethylene glycol hydrogels, and secondly, the ability to control integrin profiles and subsequently activate signalling pathways. The 'Design2Guide' platform aims to develop hydrogel-based tumour tissue mimicking systems to study cell-cell and cell-matrix interactions in people with pancreatic cancer. The research will benefit scientists in the field of tumour tissue engineering. This new, interdisciplinary field of research combines tissue engineering and cell biology (Nature Reviews Materials 2023 doi:10.1038/s41578-023-00535-3).

The importance of the new platform lies primarily in the fact that it will allow cell adhesion in tissues to be better reproduced in synthetic matrices in the future, thus enabling new insights for research into cancer therapies.

Article from "idw - Informationsdienst Wissenschaft" from 01/08/2023