Triggering the landslide: the tumor-promotional effects of myofibroblasts

Cancers become significantly more dangerous when the tumor progresses from in situ, or contained, to an invasive state, in which the cancer cells acquire the ability to pass through the surrounding basement membrane (BM), a specialized extracellular matrix (ECM) that provides structure and contextual information to the underlying tissue. While the majority of tumors are carcinomas, derived from epithelial cells, it is the stromal cells surrounding the epithelial-derived tumor cells, including fibroblasts and myofibroblasts, vasculature, and immune cells, that are largely responsible for the production and remodeling of the ECM. Here, we will discuss myofibroblasts as key effectors of tumor progression, focusing on recent advances in breast and pancreatic carcinoma, showing how myofibroblasts may function properly in normal tissue remodeling and wound-healing processes, how in the tumor context they can drive cancer invasion and metastasis, and how the pathogenic functions of myofibroblasts may be targeted therapeutically.