Join us in Philadelphia from Sept. 25-27th for our "Together We Will" Weekend: - Register today!

The Desmoid Tumor Research Foundation

September 2018

Growth rate and myofibroblast differentiation of desmoid fibroblast-like cells are modulated by TGF-beta signaling

Author Information

Enzo MV(1), Cattelan P(1), Rastrelli M(2), Tosi A(3), Rossi CR(2)(4), Hladnik U(1), Segat D(5).

(1)Genetics Unit, "Mauro Baschirotto" Institute for Rare Diseases (B.I.R.D.), Via B. Bizio, 1, Costozza di Longare, 36023, Costozza di Longare, VI, Italy. (2)Melanoma and Sarcoma Unit, Veneto Institute of Oncology, IOV-IRCSS, 35128, Padua, Italy. (3)Pathology Unit, Veneto Institute of Oncology, IOV-IRCSS, 35128, Padua, Italy. (4)Dept of Surgical Oncological and Gastroenterological Science, University of Padua, 35128, Padua, Italy. (5)Genetics Unit, "Mauro Baschirotto" Institute for Rare Diseases (B.I.R.D.), Via B. Bizio, 1, Costozza di Longare, 36023, Costozza di Longare, VI, Italy.

Publication

Histochem Cell Biol

Summary

The aim of this study was to investigate the response of DF cells to microenvironmental factors such as inflammatory and growth factors or hormones. We observed that the inflammatory cytokine, transforming growth factor-beta (TGF-beta1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a beta-catenin mutation. The role of TGF-beta1 in cell growth and myogenic differentiation of in vitro cultures of primary DF cells and normal fibroblasts was investigated by gene and protein expression analyses. We demonstrated that TGF-beta1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-beta1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-beta1 inducing the DF myofibroblast differentiation, implying that the intercellular communications have an important role on the DF myofibroblast behavior. We observed the formation of an increased stress-fiber pattern in DF cells with increased projected cell area and stronger cell-cell contacts in presence of TGF-beta1. These results demonstrated that TGF-?1 plays a crucial role in the DF cells growth and, together with cell-cell interactions, in DF myofibroblast conversion; we also highlighted that the cellular sensitivity to this cytokine was an intrinsic feature of the DF cells.

View Abstract