METALLOPROTEINASES IN TUMOR PROGRESSION - THE CONTRIBUTION OF MMP-9

Many enzymes capable of proteolytic degradation of extracellular matri x and basement membranes have been implicated in tumor progression, in cluding the matrix metalloproteinases, cathepsins, plasminogen activat ors, and heparanase. Matrix metalloproteinases, a family of zinc-depen dent proteases, participate in several steps in tumor progression, inc luding invasion, metastasis, and angiogenesis. In this review, we will give a brief overview of this protease family, and we will review in vitro and in vivo evidence implicating a particular metalloproteinase, the 92-kD type IV collagenase/gelatinase (MMP-9 or gelatinase B), as well. as other metalloproteinases, in cancer progression. Finally, usi ng recent studies from our laboratory, we will demonstrate the importa nce of both tumor cell and host stromal cell production of MMP-9 in tu mor progression.