Desmoid-type fibromatosis (DF) is a rare benign tumor characterized by a fibroblastic features and a variable and often unpredictable clinical course. Indeed desmoid tumors show differences in growth rate, spontaneous regression, and recurrences. Although it is known that desmoid tumours are associated with Wnt pathway alterations there is no perfect correlation between either beta catenin or APC mutations and disease penetrance or recurrence. Furthermore the frequent association of this type of tumour with local and repeated injuries, the spontaneous regression and stabilization of disease progression are even more difficult to explain, suggesting the involvement of other altered signaling or the aberrant response of the DF cells to external environmental stimuli (Escobar C. et al, 2012). This might explain why efficacy of single pharmaceutical agents is limited, but also suggests that other pathways might represent additional targets for inhibitor therapy in this disease (Mignemi NA et al., 2012). These findings and the peculiar elements of desmoid tumors such as the fibroblast proliferation and the massive amounts of extracellular matrix remind the characteristics of wound healing and fibrosis process. Numerous studies on fibrotic diseases and on wound-healing processes highlighted how the cell spreading and the cell adhesion complexes could play an important role in mediating the TGF-β stimulus by modulating the intracellular signal transduction pathways. In this project we aim to investigate the type and the role of cellular communications with extracellular matrix protein (ECM) in desmoid tumors cells for the translation of matrix-derived signals into cellular response. In particular we will study the role of cell adhesion receptor, and of focal-adhesion formation in the induction of stress-fiber assembly and myofibroblastic differentiation after TGF-β stimulus.
LAY VERSION OF ABSTRACT- “In vitro study of the involvement of cell-cell and cell-matrix and focal adhesion formation in desmoid-type fibromatosis myofibroblastic differentiation under pro-inflammatory stimuli.”
