This project aims to understand the mechanisms by which tumour cells recruit and activate stromal cells and the impact of stromal activation on tumour progression and metastasis and the response to therapies

A key event in the invasion and metastasis of breast cancers is their ability to recruit an activated stroma. A key mechanism for achieving this is the ability of tumours to recruit mesenchymal stem cells (MSCs) from the bone marrow. MSCs have two main functions. First, they can differentiate to form a number of unique mesenchymal cell types including osteocytes, chondrocytes, myoblasts, adipocytes, pericytes and fibroblasts. Second, MSCs secrete a range of bioactive molecules that modulate the microenvironment and surrounding cell types.

We are studying the cross-talk between tumour cells and MSCs in the tumour stroma, both during progression of the primary tumour and at the time of metastatic growth at a secondary site, with a focus on differentiation and activation of MSCs to towards a cancer associated fibroblasts phenotype. In particular, we aim to understand how metastatic tumour cells recruit and activate stromal cells to create a favourable microenvironment for their progression into a metastatic cancer. In addition, it has been well documented that the extent of stromal activation varies widely between individual breast cancers but little is known about the mechanisms underlying this heterogeneity. As part of this project we are investigating the molecular basis by which tumour cells define the type, architecture and activation status of the recruited stroma and how this heterogeneity impacts on tumour progression and metastasis and the response of patients to endocrine, chemotherapeutic and targeted therapies.