TIMP-2 decreases the invasive potential of MCF-7 and MDAMB-231 cells independent of MMP inhibition

Tissue Inhibitors of Metalloproteinases (TIMPs) are the natural inhibitors of Matrix Metalloproteinases (MMPs), a family of proteins primarily responsible for Extracellular Matrix (ECM) remodeling. TIMP-2 is a special member of the TIMP family as it is both an inhibitor and promoter of MMP activity, and can also bind the cell surface and signal inside the cell to influence cell behavior. In this study, MDAMB-231 and MCF-7 breast cancer cells were treated with physiological concentration of TIMP-2, which decreased the invasive potential of both cell lines. This was independent of MMP inhibition, and instead a decrease in the expression and secretion of MMP-2 was observed. By using a TIMP-2 mutant, it is likely that the C-terminal domain of unbound TIMP-2 mediated this effect. This study highlights the pleiotropic functions of TIMP-2 and how inhibition of MMP activity is not a requirement for the functions of this protein