CYSTATIN C EXPRESSION AND B16 MELANOMA METASTASIS

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The long-term goal of this project is to understand the role of cysteine proteinases and their inhibitors in tumor cell metastasis. Metastasis is the major cause of cancer mortality and a dominant feature of metastatic cells is their ability to invade normal tissues via proteolytic events. This proposal will look at the cysteine proteinase inhibitor cystatin C as a potential anti-metastatic agent. The hypothesis to be tested is that cystatin C can block invasion by B16 melanoma cells due to inhibition of cysteine proteinase activity. The specific aims for this proposal are: 1. Creation of a mouse cystatin C expression plasmid driven by a metallothionein promoter that will permit overexpression of cystatin C in response to zinc. 2. Measurement of the expression levels of cystatin C in both untransfected and expression plasmid transfected B16 melanoma cell lines in response to zinc. 3. In vitro invasion parameters for transfected B16 melanoma cells will be measured both with and without zinc induction of transfected cystatin C. Overexpression of cystatin C will determine which steps of tumor cell metastasis require cysteine proteinase activity to occur.