Proteolytic enzymes have been implicated in dissolution of the extracellular matrix as tumor cells move into other tissues during the metastatic cascade. One of the proteolytic enzymes that has been correlated with metastatic capability is cathepsin B or a cathepsin B-like cysteine proteinase (CB). We are studying the role of CB in tumor metastasis by isolating the enzyme from normal liver and several tumor types from both humans and mice. The physical and kinetic properties of the tumor enzymes are being compared to cathepsin B from normal liver isolated in our laboratory and to published observations on cathepsin B isolated from several normal tissues. We have now demonstrated that tumors and in particular metastatic tumors have CB associated with the plasma membrane as well as with the lysosomes. In further studies we plan to isolate and characterize the plasma membrane-associated CB. Purified CB enzymes are being and will be used for development of polyclonal and monoclonal antibodies. The purified enzymes and the antibodies will be used for in vitro studies of invasion following digestion of extracellular matrix components and movement of tumor cells through human amnion basement membrane. These studies should further our knowledge of the potential role of cysteine proteinases in tumor metastasis. (B)
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