Pancreatic cancer-associated myofibroblasts: a review

Pancreatic cancer is a very deadly disease, with no effective therapy currently employed in clinical practice, highlighting the urgent need for new therapeutic strategies. Cancer cells represent a minority within the pancreatic tumor, which is characterized by a pronounced stromal compartment. As fibrosis is characteristic of pancreatic ductal adenocarcinoma, the cell population of particular interest is the pancreatic cancer-associated myofibroblast population, observed to be the main extracellular matrix producers. Recent studies revealed a plurality of myofibroblast functions in the pancreatic tumor, beyond their role in matrix secretion: they were noted to promote cancer cell proliferation and invasiveness in in vitro and in vivo studies, and have been described as potential prognostic biomarkers, along with stromal collagen content. Moreover, myofibroblasts were found in precancerous pancreatic lesions, and may thus be involved in pancreatic carcinogenesis. Paradoxically, depletion of myofibroblasts had detrimental effects on the outcome in an in vivo study, and their precise role in the disease remains unclear. This review summarizes for the first time studies on pancreatic cancer-associated myofibroblasts, focusing on the origin, function, biomarker potential, and heterogeneity of these cells in the pancreatic tumor, aiming to elucidate their role in pancreatic cancer progression.