Multifunctional role of pancreatic stellate cells in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths with a dismal 5-year survival rate of only 8%. PDAC is characterised by extensive desmoplasia constituting about 50–80% of the tumour volume. Activated pancreatic stellate cells (PSC) are the major cellular source for stromal collagen; these cells drive pancreatic fibrosis and progression of PDAC. PSC are known to be activated by paracrine signals from several sources including injured epithelium, cancer cells, extracellular matrix, immune cells and nerve cells. Stromal-tumour interactions are now recognised as key processes in the development and progression of PDAC. Improved understanding of the mechanisms underlying stromal-tumour interactions may be the key for the discovery of new therapeutic targets in PDAC. This review summarises current knowledge regarding the role of PSCs in cancer biology and discusses the potential for development of novel therapeutic approaches targeting factors such as dysregulated signalling pathways, the stromal reaction itself and epigenetic changes in stromal and/or cancer cells.