Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that act outside the cell to alter the environment. As implied by their name, molecules that constitute the extracellular matrix (ECM), which includes basement membranes as well as interstitial fibers, are substrates of the MMP enzyme family. Other substrates include growth, death, chemotactic, and other signaling factors, as well as proteinases and proteinase inhibitors. The ability to modulate this vast array of different types of proteins means that MMPs can be potent regulators of cellular behavior. In this chapter, we review the discovery and study of MMPs and describe the current thinking of how MMPs contribute to tumor progression, specifically the processes of invasion and metastasis. To properly understand biological functions of MMPs, in vitro and in vivo methods for their analysis have been developed. Using such analytical tools wisely requires an understanding of their limitations and possible interpretations. Despite an immense amount of research concerning this important group of proteases in cancer, as well as in other pathological and physiological conditions, there are still multiple unanswered questions; thus, we end this chapter by considering some of these.

DISCOVERY AND CHARACTERIZATION OF MMPS

In humans, the MMP family currently comprises twenty-three members, although inclusion of all mammalian as well as frog and avian MMPs bring the total known to twenty-five. These enzymes are most simply known as MMP-1 to MMP-28.