The Role of the Myofibroblast in Fibrosis and Cancer Progression

Abstract

The discovery of the myofibroblast (Gabbiani et al., Experientia 27:549–550, 1971; Tomasek et al., Nat Rev Mol Cell Biol 3:349–363,
2002) has opened a new perspective in the understanding of phenomena such as connective tissue remodeling

and epithelial–mesenchymal interactions that play crucial roles in normal and pathological processes including organ shaping
during development, tension production in pulmonary alveoli, wound contraction

, tissue deformation during fibrotic diseases and, more recently, epithelial tumor invasion or metastasis formation. The myofibroblast
has been shown to: (1) produce mechanical force, thanks to the neo-expression of a-smooth muscle actin (α-SMA), the actin
isoform typical of vascular smooth muscle cells (SMCs) (Hinz et al., J Cell Biol 157:657–663, 2002) and the formation of specialized
junctional complexes with the extracellular matrix (ECM) (Dugina et al., J Cell Sci 114:3285–3296, 2001; Goffin et al., J
Cell Biol 172:259–268, 2006), and (2) synthesize collagen type I and III (Tomasek et al., Nat Rev Mol Cell Biol 3:349–363,
2002); all these changes take place under the stimulation of local mechanical forces and of transforming growth factor b1
(TGFβ1), produced by infiltrated macrophages or local cells, in conjunction with the ectodomain A (ED-A) sequence of cellular
fibronectin (FN) (Tomasek et al., Nat Rev Mol Cell Biol 3:349–363, 2002). Thus, the myofibroblast appears as a major player
in connective tissue rearrangement.