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.
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.
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