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Modelling heterotypic cell-cell interactions in vivo at the initial stages of pancreatic cancer

Recipient: Dr Catherine Hogan

Host Institution: European Cancer Stem Cell Research Institute, Cardiff University

Title: Modelling heterotypic cell-cell interactions in vivo at the initial stages of pancreatic cancer

Type of award: 2013 Research Innovation Fund

Funding: £74,822

The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which begins when cells of the exocrine tissues of the pancreas accumulate genetic mutations, many years before symptoms appear. Using biological models that develop PDAC, we now know that mutations in the oncogene KRas are the first to occur and are required for tumour development. What remains poorly described is the biology of the very early stages of this disease once KRas mutations have been switched on. Using a model systems, researchers have shown that the majority of cells expressing mutations in KRas 'disappear' from the pancreas and only a small minority of cells stay in the tissue and develop into a tumour. I have previously shown that cells expressing KRas mutations are pushed out of a layer of normal cells via a process that is dependent on the presence of, and interaction with the normal cells. In this project I will explore whether switching on KRas mutations in pancreatic ductal cells leads to these cells being pushed out from the normal tissue, and whether this promotes tumorigenesis, which may lead to the development of new methods of identifying PDAC at the early stages.