Cystatin C as an antagonist of TGF-.beta. and methods related thereto Download HRPP SOPs Clinical Trials Find a Researcher Tech ID: 04-05 Summary - Aberrant TGF-ß signaling is often associated with tumor malignancies in humans. Scientists at the National Jewish Health have discovered that cystatin C, an extracellular protein, acts as a TGF-ß receptor antagonist and is capable of inhibiting TGF-ß signaling. Therefore, cystatin C and derivatives form the basis for drug development aimed at treating of some cancers or fibrotic/proliferative diseases regulated by TGF-ß. Potential Applications Method to regulate or prevent tumor growth and metastasis Therapies for proliferative and fibrotic diseases regulated by TGF-ß Advantages of Invention - No direct TGF-ß receptor antagonist currently exists State of Development - Our scientists have shown the following: Our scientists have shown the following in vitro : cystatin C is downregulated in human tumors Overexpression of cystatin C in highly malignant human HT1080 fibrosarcoma cells inhibits their invasion through matrices and the expression of TGF-ß-responsive genes TGF-ß treatment of 3T3-L1 fibroblasts stimulates their invasion through matrices Overexpression of cystatin C in these TGF-ß-treated cells inhibits this invasion process Cross-linking assays show that recombinant cystatin C dose-dependently inhibits the binding of TGF-ß to its cell surface receptor Other assays show that cystatin C physically interacts with the TGF-ß type II receptor but not with TGF-ß, and that cystatin C inhibits TGF-ß signaling In vivo, our scientists have found that cystatin C (and d14-CystC, a mutant of cystatin C) inhibits TGF-ß signaling and breast tumor growth in mice. Patent - U.S. Patents #7,282,477 and #7,749,958. International Patent Publication #WO2005/037221. Publications Sokol & Schiemann, Mol Cancer Res. 2004 March, 2(3):183-95. Sokol et al. (2005) Breast Cancer Res.7:R844-53. Tian & Schiemann, Transl Oncol. 2009 August 18; 2(3): 174–183. Inventors - William P. Schiemann, PhD Licensing Status - This technology is available for licensing. For Further Information, Contact: Emmanuel Hilaire, PhD Director Technology Transfer Office National Jewish Health 1400 Jackson Street, Room M206b Denver, CO 80206 Voice: 303.398.1262 Fax: 303.270.2352 HilaireE@njhealth.org