Identification of microenvironment signals that determine tumour formation in the common tumour predisposition syndrome, Neurofibromatosis Type 1

It is increasingly becoming clear that the microenvironment is key to determining whether or not a tumour will develop. We have developed a novel mouse model that has key implications for our understanding of the critical role of the microenvironment in determining whether tumour develop in patients with Neurofibromatosis Type 1 (NF1), a tumour predisposition syndrome in which patients develop multiple tumours in the nervous system. Schwann cells are the cell-of-origin for many of these tumours and the loss of the NF1 gene is the initiating event for these tumours. We have developed a unique mouse model in which we are able to track the early stages of the formation of these tumours. In this model, labeled Schwann cells lacking NF1 behave normally until the nerve is injured, when at the site of injury they develop tumours, whereas away from the injury site, they behave like normal Schwann cells following injury, in that they proliferate, aid the repair process, and then re-differentiate. Understanding the microenvironment signals which promote/suppress the formation of these tumours could have important clinical implications by identifying mechanisms to persuade the tumour cells to revert to more normal behaviour. For this project, using a combination of molecular, imaging and in vivo studies, the aim is to identify the mechanisms involved and determine the potential of developing therapeutics based on these findings.