Cystatin C: An Extracellular Antagonist of the TGF-ß Receptor. Potential Therapies for Cancer and Fibrotic Diseases
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. Patent #7,282,477. 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
Manager
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: (303) 398-1262
Fax: (303) 270-2352
[email protected]
