In order to investigate the role of type IV collagenase in tumor invasion and metastases, we have undertaken the purification, molecular cloning, enzymatic characterization, and the study of structure-function correlation of this 72 kDa metalloproteinase. We have also studied the binding of type IV collagenase to both type IV collagen and gelatin. These studies have demonstrated that enzyme binding to these substrates is independent of metal atoms and can be competed by fibronectin and fibronectin-gelatin binding domain peptides. Recent studies have focused on the transcriptional regulation of the 72 kDa collagenase Iv enzyme in both normal and human tumor cell lines as well as human tumor tissues. These studies have shown that the 72 kDa collagenase is unique among the members of the matrix metalloproteinase enzymes in the manner of its regulation by various cytokines. Also, the 72 kDa collagenase IV probes shows elevated levels in colorectal tumor tissues when compared with adjacent normal mucosa tissue. In expanding this project, we have also cloned and sequenced the human tumor cell interstitial collagenase. The tumor enzyme was found to be identical to the fibroblast collagenase, thus demonstrating definitively and for the first time that ductal epithelial cells are capable of producing this enzyme.
