A distinctive feature of tumor cells is their potential to invade surrounding tissues and metastasize through the blood and lymphatic systems to distant organs. It is well known that cancer metastasis is a highly complicated phenomenon requiring the interaction of many types of cells, enzyme activation, connective tissues, and blood vessel basement membrane. This study focuses on the inflammatory cells and the active environment in which they facilitate growth and eventual metastatic spread of neoplastic cells. Excess proteolytic activity of Human Neutrophil Elastase (HNE) is believed to cause damage to the extracellular matrix (ECM), which enhances the possibility of metastasis from a tumor cell. It is thought that tumor cells recruit inflammatory cells by using chemotactic factors and/or causing damage to the ECM. It is known that elastases bind to the membrane of the inflammatory cell, thus making it capable to cleave through the ECM, and therefore indirectly allows the tumor cells to break through the basement membrane, causing metastasis. The purpose of my study is to evaluate the effect of endogenous and pharmaceutical inhibitors of Elastase on HNE bound to the Polymorphonuclear neutrophil (PMN), a known inflammatory cell. In this study, we utilized endogenous inhibitors such as alpha-1-protease inhibitor (a-1-PI) and secretory leukocyte protease inhibitor (SLPI), as well as exogenous inhibitors such as CE2072 and 3,4-DCI inhibitor. Preliminary data show that these inhibitors work successfully on non-membrane bound HNE in a dose response manner. Chromogenic assays were performed on an optical density microplate reader, which measured activity through amidolysis initiated by the synthetic substrate N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. Results are still pending. Appropriate and pharmacological doses of these inhibitors may be helpful in preventing metastasis in patients who are in early stages of cancer. This study was supported by the Source Pharmaceuticals Grant and the Simons Grant No. 265210.