###The role of cancer cell mechanics and remodelling in engineered tumouroids
Project ID: 2228bd1053 (You will need this ID for your application)
Research Theme: Advanced Materials
UCL Lead department: Division of Surgery and Interventional Sciences
Lead Supervisor: Um,ber Cheema
Project Summary:
3D tumouroids are generated by embedding cancers cells in a biomimetic collagen scaffold and surrounding this with a biomimetic stroma containing tissue stromal cells and engineered vascular networks1. These models can be used to quantify cancer invasion and investigate the interaction of cancer with normal stromal cells at the tumour-stroma boundary1. Using cancer cell lines, it has been shown that more invasive cancer cells soften the stromal matrix, which is hypothesised to help the cells spread and metastasise, whereas less invasive cells stiffen the matrix2.
This project aims to extend our work by employing patient derived cancer and stromal cells to investigate how cancer cells remodel their tumour microenvironment. This project aims to specifically test how patient-derived cancer cells and cancer-associated fibroblasts remodel the tumour matrix, both separately and 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.
In addition to this fundamental work, 3D tumouroids will be cultured a macro-fluidic device. The action of media flow is hypothesised to enhance the functionality of the 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.