Desmoid and fibroma tumours are characterized by cell proliferation, glycosaminoglycan and collagen fibre accumulation, high levels of transforming growth factor b1 (TGFb1) and different patterns of tissue infiltration. TGFb1, which plays a central role in normal tissue homeostatic regulation, stimulates the production and secretion of ECM macromolecules, such as GAG and matrix proteins, and inhibits protease production which regulates ECM turnover. TGFb1 deregulation can be related to the invasive metastatic potential of tumour cells. In this study we report changes in cell proliferation, glycosaminoglycan (GAG) and collagen synthesis, TGFb1 mRNA expression and fibronectin levels in normal, desmoid and fibroma fibroblast cultures before and after TGFb1 stimulation. Our data showed cell proliferation, GAG and collagen synthesis, transforming growth factor b1 mRNA expression and fibronectin levels were significantly higher in desmoid than in fibroma cultures. TGFb1 treatment had no effect on cell proliferation, but increased TGFb1 mRNA expression, GAG, fibronectin and collagen synthesis in desmoid and fibroma fibroblasts. Its effects were more marked in desmoid cells. Fibronectin favours cell migration, while changes in GAG composition alter cell behaviour and ECM organization. In conclusion our data suggest that the different patterns of infiltration in desmoid and fibroma tumours are due to changes in ECM components and celleECM interactions which can be ascribed to altered TGFb1 mRNA expression and TGFb1 activity. Transforming growth factor b1 (TGFb1), which plays a central role in normal tissue homeostatic regulation, stimulates the production and secretion of ECM macromolecules, such as GAG and matrix proteins, and inhibits protease production which regulates ECM turnover [7,8]. In tumour cells TGFb1 is significantly higher than in normal cells [9] and modifies cell proliferation and differentiation, angiogenesis, collagen, proteoglycan and GAG composition [10,11], fibronectin levels and ECM polymerisation [12,13]. TGFb1 deregulation can be related to the invasive metastatic potential of tumour cells.
Desmoid and fibroma tumors differently respond to TGFbeta(1) stimulus and ECM macromolecule accumulation
LOCCI, Paola;BALDUCCI, CHIARA;LILLI, Cinzia;MARINUCCI, Lorella;BECCHETTI, Ennio;LUMARE, ELEONORA;
2007
Abstract
Desmoid and fibroma tumours are characterized by cell proliferation, glycosaminoglycan and collagen fibre accumulation, high levels of transforming growth factor b1 (TGFb1) and different patterns of tissue infiltration. TGFb1, which plays a central role in normal tissue homeostatic regulation, stimulates the production and secretion of ECM macromolecules, such as GAG and matrix proteins, and inhibits protease production which regulates ECM turnover. TGFb1 deregulation can be related to the invasive metastatic potential of tumour cells. In this study we report changes in cell proliferation, glycosaminoglycan (GAG) and collagen synthesis, TGFb1 mRNA expression and fibronectin levels in normal, desmoid and fibroma fibroblast cultures before and after TGFb1 stimulation. Our data showed cell proliferation, GAG and collagen synthesis, transforming growth factor b1 mRNA expression and fibronectin levels were significantly higher in desmoid than in fibroma cultures. TGFb1 treatment had no effect on cell proliferation, but increased TGFb1 mRNA expression, GAG, fibronectin and collagen synthesis in desmoid and fibroma fibroblasts. Its effects were more marked in desmoid cells. Fibronectin favours cell migration, while changes in GAG composition alter cell behaviour and ECM organization. In conclusion our data suggest that the different patterns of infiltration in desmoid and fibroma tumours are due to changes in ECM components and celleECM interactions which can be ascribed to altered TGFb1 mRNA expression and TGFb1 activity. Transforming growth factor b1 (TGFb1), which plays a central role in normal tissue homeostatic regulation, stimulates the production and secretion of ECM macromolecules, such as GAG and matrix proteins, and inhibits protease production which regulates ECM turnover [7,8]. In tumour cells TGFb1 is significantly higher than in normal cells [9] and modifies cell proliferation and differentiation, angiogenesis, collagen, proteoglycan and GAG composition [10,11], fibronectin levels and ECM polymerisation [12,13]. TGFb1 deregulation can be related to the invasive metastatic potential of tumour cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
