%0 Journal Article %A Chakrabarti, Jayati %A Mitra, Aparna %A Banerji, Aniruddha %A Chatterjee, Amitava %D 2006 %I Begell House %N 4 %P 667-678 %R 10.1615/JEnvironPatholToxicolOncol.v25.i4.60 %T Culture of Human Fibrosarcoma HT-1080 Cells in Presence of Fibronectin Activates MMP-2 %U https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,448422593e3e989d,5595f0cb74f6b2a7.html %V 25 %X The importance of tumor cell surface integrin receptors in regulation of matrix metalloproteinase (MMP) expression and function has been reported. Integrin-ECM ligand interaction leads to phosphorylation of focal adhesion kinase (FAK) and activation of mitogen activated protein kinase (MAPK) pathways. In this present study, we cultured human fibrosarcoma cells, HT-1080, in presence of fibronectin to study fibronectin-integrin mediated modulation of MMP activity. Methods: HT-1080 cells were cultured in serum free medium (SFCM) in presence of fibronectin, SFCM was collected, and gelatin zymography was performed. Western blot and immunocytochemistry were performed with HT-1080 cells cultured in presence of fibronectin. Results: Culture of HT-1080 cells in presence of 50 μg/1.5 ml fibronectin led to expression of pro-MMP-9 and activation of MMP-2 within 1 hr. When HT-1080 cells were treated with PI-3K inhibitor (LY294002) and grown in presence of fibronectin, MMP-2 activation was partially inhibited, but when cells were treated with ERK inhibitor (PD98059) and grown in presence of fibronectin, MMP-2 activation was almost completely inhibited. Tyrosine phosphorylation of FAK and ERK were increased in HT-1080 cells grown in presence of fibronectin. Processing of MT1-MMP was also observed in HT-1080 cells grown in presence of fibronectin. The reorganization of actin filaments in fibronectin treated HT-1080 cells was also noticeable. Conclusions: Our findings indicate that culture of HT-1080 cells in SFCM in presence of fibronectin perhaps generates a signaling cascade that leads to expression of pro-MMP-9 and activation of MMP-2 within 1 hr. The signaling pathway activated seems to be the FAK/ERK pathway. %8 2007-02-02