Stars and stripes in pancreatic cancer: role of stellate cells and stroma in cancer progression

Pancreatic cancer is a devastating disease with an unacceptably high mortality to incidence ratio. Traditional therapeutic approaches such as surgery in combination with chemo- or radiotherapy have had limited efficacy in improving the outcome of this disease. Up until just under a decade ago, the prominent desmoplastic reaction which is a characteristic of the majority of pancreatic ductal adenocarcinomas (PDAC) had been largely ignored. However, since the identification of the pancreatic stellate cell (PSC) as the key cell responsible for the production of the collagenous stroma in PDAC, increasing attention has been paid to the role of the stromal reaction in pancreatic cancer pathobiology. There is now compelling evidence that PSCs interact not only with cancer cells themselves, but with several other cell types in the stroma (endothelial cells, immune cells, and possibly neuronal cells) to promote cancer progression. This review summarizes current knowledge in the field about the influence of PSCs and the stromal microenvironment on cancer behavior and discusses novel therapeutic approaches which reflect an increasing awareness amongst clinicians and researchers that targeting cancer cells alone is no longer sufficient to improve patient outcome and that combinatorial treatments targeting the stroma as well as the cancer cells will be required to change the clinical course of this disease.