Douglas Hanahan, Robert A. Weinberg. Hallmarks of cancer: the next generation. Cell, Volume 144, Issue 5, p646–674, 4 March 2011
Fibroblasts are found in various proportions across the spectrum of carcinomas, constituting in many cases the preponderant cell population of the tumor stroma. The term «cancer-associated fibroblast» subsumes at least two distinct cell types: (1) cells with similarities to the fibroblasts that create the structural foundation supporting most normal epithelial tissues and (2) myofibroblasts, whose biological roles and properties differ markedly from those of tissue-derived fibroblasts. Myofibroblasts are identifiable by their expression of α-smooth muscle actin (SMA). They are rare in most healthy epithelial tissues, although certain tissues, such as the liver and pancreas, contain appreciable numbers of α-SMA-expressing cells. Myofibroblasts transiently increase in abundance in wounds and are also found in sites of chronic inflammation. Although beneficial to tissue repair, myofibroblasts are problematic in chronic inflammation, contributing to the pathological fibrosis observed in tissues such as lung, kidney, and liver.
Recruited myofibroblasts and reprogrammed variants of normal tissue-derived fibroblastic cells have been demonstrated to enhance tumor phenotypes, notably cancer cell proliferation, angiogenesis, and invasion and metastasis; their tumor-promoting activities have largely been defined by transplantation of cancer-associated fibroblasts admixed with cancer cells into mice, and more recently by genetic and pharmacologic perturbation of their functions in tumor-prone mice. Because they secrete a variety of extracellular matrix components, cancer-associated fibroblasts are implicated in the formation of the desmoplastic stroma that characterizes many advanced carcinomas. The full spectrum of functions contributed by both subtypes of cancer-associated fibroblasts to tumor pathogenesis remains to be elucidated.