Fig. 6.

Schematic model of TIMP-2’s biphasic effects on cellular behavior. Regardless of cell type, the addition ALA + TIMP-2 conditioned media results in global MMP inhibition. This is likely achieved by the upregulation of MMP inhibiting proteins such as RECK via established MMP independent signaling pathways such as α3β1 integrins (middle path). Decreases in MMP activity is concomitant with decreased cellular invasiveness. In non-invasive cell types that produce relatively low levels of active MMPs, the addition of TIMP-2 facilitates MMP activation and provides a mechanism for these cells to increases their cellular invasiveness. Conversely, highly invasive MDA-MB-231 cells, which already produce high levels of active MMPs, TIMP-2 inhibits MMP activity resulting in decreased invasiveness. CM; conditioned media