The role of cancer cell mechanics and remodelling in engineered tumouroids

Project ID: 2228cd1342 (You will need this ID for your application)

UCL Lead department: Division of Surgery and Interventional Sciences

Project Summary:

3D tumouroids are generated by embedding cancers cells in biomimetic collagen scaffolds and surrounding these with a biomimetic stroma containing tissue stromal cells and engineered vascular networks. These models can be used to quantify cancer invasion and investigate the interaction of cancer with stromal cells at the tumour-stroma boundary. Using cancer cell lines, we have shown that invasive cancer cells soften the matrix, which helps the cells spread and metastasise, whereas less invasive cells stiffen the matrix. We now have a clear understanding of how cancer-associated fibroblasts play a role in matrix remodelling and how this directly effects cancer invasion.

In collaboration with colleagues from engineering, this project aims to extend our work by employing matched patient derived cancer and stromal cells to investigate how cancer cells interact with stromal cells to remodel their tumour microenvironment in synergy. In doing so, the role of cell-generated active forces will be segregated from the matrix-remodelling to decipher a mechanical role for cancer cells. Samples from anonymised patients will be used to grow cancer cells and cancer associated fibroblasts. It will be possible to concord with patient cancer progression in this way.

3D tumouroids will be cultured in macro-fluidic device to study the action of media flow to enhance the functionality of engineered vasculature, which will impact the stiffness and material properties of the tumour microenvironment. The project involves employing biological assays, mechanical characterisation technology and advanced light imaging techniques.

This work will further our understanding of how cancer adapts the tumour micro-environment as it invades and metastasises, but will allow us to test mechanisms to target this behaviour and potentially stop cancer progression. The development of patient derived tumouroids will allow for the development of models of cancer to test potentially therapies and their efficacy in a personalised manner.