Culture of human breast cancer cells (MCF-7) in presence of fibronectin in serum free medium activates MMP-2 and MMP-9

Fibronectin and its integrin receptors play important roles in tumor development, affecting cell survival, proliferation and migration. The alpha 5 beta 1 integrin interacts with the central cell adhesive region of fibronectin and requires both the RGD and synergy sites for maximal binding. MMPs, a family of zinc dependent endopeptidases, are capable of digesting the different components of the Extra Cellular Matrix(ECM) and basement membrane. Binding of ECM to integrins modulates expression and activity of the different MMPs. Our experimental findings, demonstrate that cultivation of human breast cancer cells MCF-7 in serum free medium in presence of fibronectin upregulates the activity of MMP-2 and MMP-9. Blocking of alpha 5 beta 1 integrin with anti-alpha 5 monoclonal antibody inhibits the fibronectin-induced MMP activation response appreciably. This strongly indicates alpha 5 beta 1 mediated signaling events in activation of MMP-2 and MMP-9. Tyrosine phosphorylation of FAK, ERK and PI-3K and the nuclear translocation of ERK and NF-kappa B upon fibronectin binding demonstrate possible participation of the FAK/PI-3K/ERK signaling pathways in the regulation of MMP-2 activity.