ROLE OF STROMELYSIN 1 IN SQUAMOUS CELL CARCINOMA

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The focus of this proposal is to define the functional role of the matrix metalloprotease (MMP) Stromelysin-1 in squamous cell carcinoma progression. Stromelysin-1 is a major extracellular matrix (ECM) degrading proteinases implicated in a variety of normal and pathological cellular processes including tumor cell invasion. There is focused attention on defining the particular roles of individual MMP in order to appropriately modulate their activity in a clinical setting with the use of MMP inhibitors. Understanding not only the role of individual MMPs in tumor progression, but additionally the distinct roles of host/stromal and tumor MMP expression is a fundamental unanswered question the matrix protease field. We have evidence that stromelysin-1 expression can play dual roles during tumor progression, meaning that expression of stromelysin-1 during early stages of tumor progression is protective whereas tumor expression of stromelysin-1 is intimately involved in generating an invasive phenotype in squamous cell carcinoma. Current experimental cancer therapy models include the use of MMP inhibitors. Thus, we need to well define the role of stromelysin-1 at each stage of tumor progression in order to predict how loss of stromelysin-1 will effect tumor development and invasiveness. The studies outlined in the research proposal will provide novel insight into the role of Stromelysin-1 during tumor progression and provide an in vivo model for testing of MMP inhibitors in a clinical setting.