Cystatin c as an antagonist of tgf-beta and methods related thereto

Abstract

Disclosed are Cystatin C (CysC) homologues, including CystC homologues that act as antagonists or inhibitors of transforming growth factor-β (TGF-β). Also disclosed are methods to identify CystC homologues that are antagonists or inhibitors of TGF-β and compositions and therapeutic methods using CystC and homologues thereof to regulate the activity of TGF-β, and TGF-β-mediated tumor malignancy and invasion and other TGF-β-mediated fibrotic or proliferative conditions and diseases.

1 .- 34 . (canceled) 
     
     
         35 . A method to increase TGF-β activity, comprising inhibiting the ability of Cystatin C to regulate TGF-β activity. 
     
     
         36 . The method of  claim 35 , comprising contacting a TGF-β receptor with a Cystatin C homologue that is a competitive inhibitor of Cystatin C. 
     
     
         37 . The method of  claim 35 , comprising contacting a TβRII receptor with a Cystatin C homologue that is a competitive inhibitor of Cystatin C. 
     
     
         38 . The method of  claim 35 , comprising contacting Cystatin C with a compound that reduces the ability of Cystatin C to bind to or activate TβRII. 
     
     
         39 . The method of  claim 38 , wherein the compound is a soluble TβRII receptor with a decreased affinity for TGF-β that binds to Cystatin C. 
     
     
         40 . The method of  claim 38 , wherein the compound binds to Cystatin C and inhibits the ability of Cystatin C to bind to TβRII. 
     
     
         41 . The method of  claim 40 , wherein the compound does not inhibit the ability of Cystatin C to inhibit cysteine proteases. 
     
     
         42 . The method of  claim 40 , wherein the compound is an antibody, an antigen binding fragment of an antibody, or a binding partner. 
     
     
         43 .- 51 . (canceled)