Primary epithelial tumor metastasis requires cells to switch from a two-dimensional environment to proliferating at accelerated rates within the dense three-dimensional extracellular matrix (ECM) composed largely of type I collagen and cross-linked fibrin. Tumor proliferation requires in-depth remodeling of the ECM, a process that occurs in a spatially and temporally controlled fashion and involves tightly regulated protease and protease inhibitor activity. Although the role of ECM in cancer invasion is well characterized, how the cells can proliferate in the presence of strong antigrowth signals has been unclear. In the July 11 Cell, Kevin B. Hotary and colleagues at the University of Michigan identify a growth factor that enables cancer cells to defeat 3-D ECM control (Cell, 114:33-45, 11 July, 2003).