Unraveling the role of proteases in cancer

Investigators have been studying the expression and activity of proteases i n the final steps of tumor progression, invasion and metastasis, for the pa st 30 years. Recent studies, however, indicate that proteases are involved earlier in progression, e.g., in tumor growth both at the primary and metas tatic sites. Extracellular proteases may co-operatively influence matrix de gra- dation and tumor cell invasion through proteolytic cascades, with indi vidual proteases having distinct roles in tumor growth, invasion, migration and angiogenesis. In this review, we use cathepsin B as an example to exam ine the involvement of proteases in tumor progression and metastasis. We di scuss the effect of interactions among tumor cells, stromal cells, and the extracellular matrix on the regulation of protease expression. Further eluc idation of the role of proteases in cancer will allow us to design more eff ective inhibitors and novel protease-based drugs for clinical use. (C) 2000 Elsevier Science B.V. All rights reserved.