Locci Paola, Balducci Chiara, Lilli Cinzia, Marinucci Lorella, Becchetti Ennio, Dolci Claudia, Calastrini Carla, Lumare Eleonora, Stabellini Giordano
Department of Experimental Medicine and Biochemical Science, University of Perugia, Italy.
Biomed Pharmacother. 2007 Feb-Apr;61(2-3):131-6. doi: 10.1016/j.biopha.2006.09.011. Epub 2006 Nov 16.
Desmoid and fibroma tumours are characterized by cell proliferation, glycosaminoglycan and collagen fibre accumulation, high levels of transforming growth factor beta(1) (TGFbeta(1)) and different patterns of tissue infiltration. TGFbeta(1) is related to extracellular matrix (ECM) composition which, in turn, regulates cell functions and cell migration. In this study we report changes in cell proliferation, glycosaminoglycan (GAG) and collagen synthesis, TGFbeta(1) mRNA expression and fibronectin levels in normal, desmoid and fibroma fibroblast cultures before and after TGFbeta(1) stimulation. Our data showed cell proliferation, GAG and collagen synthesis, transforming growth factor beta(1) mRNA expression and fibronectin levels were significantly higher in desmoid than in fibroma cultures. TGFbeta(1) treatment had no effect on cell proliferation, but increased TGFbeta(1) 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 cell-ECM interactions which can be ascribed to altered TGFbeta(1) mRNA expression and TGFbeta(1) activity.
韧带样瘤和纤维瘤的特征在于细胞增殖、糖胺聚糖和胶原纤维积累、高水平的转化生长因子β1(TGFβ1)以及不同的组织浸润模式。TGFβ1与细胞外基质(ECM)组成有关,而细胞外基质又调节细胞功能和细胞迁移。在本研究中,我们报告了在TGFβ1刺激前后,正常、韧带样瘤和纤维瘤成纤维细胞培养物中细胞增殖、糖胺聚糖(GAG)和胶原合成、TGFβ1 mRNA表达以及纤连蛋白水平的变化。我们的数据显示,韧带样瘤培养物中的细胞增殖、GAG和胶原合成、转化生长因子β1 mRNA表达以及纤连蛋白水平显著高于纤维瘤培养物。TGFβ1处理对细胞增殖没有影响,但增加了韧带样瘤和纤维瘤成纤维细胞中TGFβ1 mRNA表达、GAG、纤连蛋白和胶原合成。其作用在韧带样瘤细胞中更为明显。纤连蛋白促进细胞迁移,而GAG组成的变化会改变细胞行为和ECM组织。总之,我们的数据表明,韧带样瘤和纤维瘤肿瘤不同的浸润模式是由于ECM成分和细胞-ECM相互作用的变化,这可归因于TGFβ1 mRNA表达和TGFβ1活性的改变。