Specific recognition of cell-surface molecules with other cells or extracellular matrix (ECM) is fundamental for cellular motility, reorganization, and proliferation. To carry out these actions, cells often displace space previously occupied by cells or the ECM, thus proteolysis may be required. More functionally in different model systems, integrin-mediated interaction of cells with ECM influences or directs cell growth, differentiation and survival via specific intracellular signaling pathways (1–3). Thus, the interplay between binding of integrins (and other surface molecules) with ECM and the proteolysis of ECM must be highly orchestrated. The mechanism of degradation of ECM for these physiological purposes is under stringent control, turning on only when appropriate signals are in place for a subsequent function. The importance of ECM-degrading proteases in such interactions was shown recently in transgenic animals expressing an autoactivated, ECM-degrading metalloprotease targeted to mammary epithelial cells. These epithelial cells underwent early apoptosis near the end of pregnancy. When these transgenic mice were crossed with mice overexpressing an endogenous inhibitor of the protease, early apoptosis was not observed (4). These results emphasize the importance of proteinases and their inhibitors in regulating the functions of cell-ECM interactions.