Role of the microenvironment in chronic pancreatitis and pancreatic cancer

Chronic pancreatitis, an inflammatory disease of the exocrine pancreas, has been reported to be a major risk factor for the development of pancreatic ductal adenocarcinoma. Evidence from pre-clinical mouse models has shown that both diseases share a common origin in the digestive enzyme-producing acinar cells, through acinar to ductal metaplasia. Moreover, both diseases are characterised by the presence of an abundant stroma, the components of which include activated pancreatic stellate cells and immune cell infiltrates, which signal to epithelial cells through the production of cytokines and chemokines. In this review we explore the links between chronic pancreatitis and pancreatic ductal adenocarcinoma, with particular reference to the role of the microenvironment in both diseases. A better understanding of the nature of the epithelial and stromal changes, as well as their interactions, has led to trialling novel therapeutic strategies for the prevention and/or treatment of pancreatic cancer.