The protease consortium: An alliance to advance the understanding of proteolytic enzymes as therapeutic targets for cancer
✍ Scribed by Vincent L. Giranda; Lynn M. Matrisian
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 61 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0899-1987
No coin nor oath required. For personal study only.
✦ Synopsis
The contribution of extracellular proteolytic activity to tumor growth, invasion, and metastasis has been under investigation for more than 20 yr. In particular, the matrix metalloproteinases (MMPs), serine plasminogen activators, and cathepsins have been shown to enhance tumor progression in diverse systems. Therapeutic intervention by use of protease inhibitors is just being realized and is currently led by phase III clinical trials of MMP inhibitors for a variety of tumor types. But what are the contributions of the metalloproteinases, relative to the other classes of proteinases, to these tumors? Do extracellular proteinases cooperatively in¯uence matrix degradation and tumor cell invasion, or do individual proteinases have distinct in¯uences on tumor growth, invasion, migration, angiogenesis, etc? The answers to these questions are being sought by the Protease Consortium, a group of investigators from academic and pharmaceutical institutions supported by an ``Activities to Promote Research Collaborations'' grant from the National Cancer Institute.
The investigators in the Protease Consortium have made signi®cant contributions to understanding the role of speci®c proteases in tumor progression. These investigators are joined by scientists from Abbott Laboratories, where investigations on small-molecule inhibitors of metalloproteinases, plasminogen activators, and cathepsins are under way. These researchers will combine their talents and reagents to design proof-of-principle experiments to examine the role of the various protease classes individually as well as collectively in established animal models for cancer. The consortium will design and execute experiments over the next 2.5 yr and will hold four meetings during that period to facilitate experiments and discuss results.
The ®rst meeting, held at Vanderbilt University March 22±23, 1999, and hosted by the consortium chair, Lynn Matrisian (Vanderbilt University, Nashville, TN) was designed to select appropriate animal models for subsequent studies. Before the meeting, consortium members performed comprehensive searches the literature about in vivo models used