Images of Cleavage: Tumor Proteases in Action

Abstract

The roles of proteases in cancer are now known to be much broader than simply degradation of extracellular matrices during tumor invasion and metastasis. Furthermore, proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, and endothelial cells) as well as tumor cells are recognized to contribute to proteolytic pathways critical to neoplastic progression. Although increased expression of proteases at the level of transcripts and protein has been observed in many tumors, the functional roles of proteases remain to be determined. Novel techniques for imaging activity of proteases, both in vitro and in vivo, are available as are selective imaging probes and substrates that allow discrimination of the activity of one class of protease from another or one individual protease from another. In this chapter, we describe in vitro models and assays for the functional imaging of proteases and proteolytic pathways. These models and assays can serve as screening platforms for the identification of pathways that are potential therapeutic targets and for further development of technologies and imaging probes for in vivo use. Such uses might include diagnosis and patient follow-up during the course of therapies that alter protease activities, perhaps even providing the crucial data needed to alter the course of treatment and/or the therapies used.