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. Patents #7,282,477 and #7,749,958.  International Patent Publication #WO2005/037221.

Publications

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
HilaireE@njhealth.org

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