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Metastasis is the most difficult aspect of cancer treatment.We have been working with natural inhibitors of metastasis, the cystatins.Cystatins are cysteine protease inhibitors which belong to a widely expressed superfamily of proteins.Typically most cancers over-express cysteine proteases and hence tumor cystatin/cysteine protease ratios decline during tumor development.We showed that over-expression of cystatin C was able to markedly suppress melanoma metastasis in an animal model.