Research Involvement Network Opportunity: Understanding how physical forces shape the behaviour of pancreatic tumours
Help to shape a project looking at how tumour cells response to physical forces in their surrounding environment
Dr Konstantina Nikolatou at King’s College London and The Francis Crick Institute in London is looking for members of the Research Involvement Network to help her in the development of her project. She would like feedback on the lay summary of her work before applying for funding from Pancreatic Cancer UK.
Within our bodies, cells are surrounded by and adhere onto a mixture of proteins. This protein network, or matrix, is a unique source of information for the cells in the form of chemical signals. It is also a scaffold, and cells can sense its physical properties (i.e. if it is stiff or soft, smooth or patterned, more or less viscous). We know that the cell- matrix interaction alters how cells behave. In the recent years we have started to understand how cells sense physical forces from their matrix and how they turn these mechanical inputs into a biological response.
This interaction becomes particularly relevant in the case of pancreatic cancer. The matrix is a major component of pancreatic tumours and has been described to undergo dramatic changes in its physical properties during disease progression. We want to better understand how cancer cells specifically respond to the mechanical changes of the tumour matrix and how they adapt to them.
As such, my hypothesis is that the altered mechanics of the diseased matrix will play a significant role in supporting pancreatic tumour progression. For example, we already know that increased matrix stiffness can make tumours more aggressive, as it allows cancer cells to move. This is a crucial step during metastasis formation. One not so well explored mechanical property of the matrix is viscoelasticity. Viscoelasticity is the ability of the matrix to act as both a solid and a liquid. A rubber band has a purely elastic behaviour- you pull it and when you stop applying forces, it immediately bounces back to its original shape. A toy-slime, on the other hand, has a viscoelastic behaviour so it will undergo permanent change in its shape if you press on it.
In the lab we have the technology that allows us to make our own matrices and control their mechanical properties independently from each other. We have already seen that pancreatic tumour cells will behave differently if grown in matrices that are more viscoelastic than elastic, while the other mechanical properties remain unchanged. This suggests that there are proteins that can sense and respond specifically in increased viscoelasticity. We want to find these proteins, understand how they become activated and what their activity means for cellular function.
If you would like to take part, please contact the Research Team with the involvement reference ‘Pancreatic physical forces study’. We will then email you the lay summary and any specific questions Dr Nikolatou would like you to consider. Please return your responses to the us by Friday 24th March 2023.