Abstract
Desmoid-like fibromatosis (DF) is a rare myofibroblastic benign tumor, often associated with local and repeated injuries, spontaneous regression and stabilization of disease progression suggesting the involvement of altered Wnt/β-catenin signaling activation and/or aberrant response of the DF cells to external environmental stimuli. 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-β (TGF-β1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a β-catenin mutation. The role of TGF-β1 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-β1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-β1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-β1 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-β1. These results demonstrated that TGF-β1 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.
| Original language | English |
|---|---|
| Number of pages | 16 |
| Journal | Histochemistry and Cell Biology |
| DOIs | |
| Publication status | E-pub ahead of print - Sep 1 2018 |
Fingerprint
Keywords
- Cells growth
- Desmoid-like fibromatosis (DF)
- Myofibroblast differentiation
- TGF-β1
- Wnt pathway
ASJC Scopus subject areas
- Histology
- Molecular Biology
- Medical Laboratory Technology
- Cell Biology
Cite this
Growth rate and myofibroblast differentiation of desmoid fibroblast-like cells are modulated by TGF-β signaling. / Enzo, Maria Vittoria; Cattelan, Paola; Rastrelli, Marco; Tosi, Annalisa; Rossi, Carlo Riccardo; Hladnik, Uros; Segat, Daniela.
In: Histochemistry and Cell Biology, 01.09.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Growth rate and myofibroblast differentiation of desmoid fibroblast-like cells are modulated by TGF-β signaling
AU - Enzo, Maria Vittoria
AU - Cattelan, Paola
AU - Rastrelli, Marco
AU - Tosi, Annalisa
AU - Rossi, Carlo Riccardo
AU - Hladnik, Uros
AU - Segat, Daniela
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Desmoid-like fibromatosis (DF) is a rare myofibroblastic benign tumor, often associated with local and repeated injuries, spontaneous regression and stabilization of disease progression suggesting the involvement of altered Wnt/β-catenin signaling activation and/or aberrant response of the DF cells to external environmental stimuli. 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-β (TGF-β1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a β-catenin mutation. The role of TGF-β1 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-β1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-β1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-β1 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-β1. These results demonstrated that TGF-β1 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.
AB - Desmoid-like fibromatosis (DF) is a rare myofibroblastic benign tumor, often associated with local and repeated injuries, spontaneous regression and stabilization of disease progression suggesting the involvement of altered Wnt/β-catenin signaling activation and/or aberrant response of the DF cells to external environmental stimuli. 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-β (TGF-β1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a β-catenin mutation. The role of TGF-β1 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-β1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-β1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-β1 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-β1. These results demonstrated that TGF-β1 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.
KW - Cells growth
KW - Desmoid-like fibromatosis (DF)
KW - Myofibroblast differentiation
KW - TGF-β1
KW - Wnt pathway
UR - http://www.scopus.com/inward/record.url?scp=85052785899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052785899&partnerID=8YFLogxK
U2 - 10.1007/s00418-018-1718-1
DO - 10.1007/s00418-018-1718-1
M3 - Article
AN - SCOPUS:85052785899
JO - Histochemistry and Cell Biology
JF - Histochemistry and Cell Biology
SN - 0948-6143
ER -