Wnt Antagonists and Methods of Treatment and Screening

Abstract

The present invention relates to compositions comprising Wnt antagonists and methods of treating Wnt-associated diseases and disorders, such as cancer, inducing differentiation, and reducing the frequency of cancer stem cells, as well as novel methods of screening for such Wnt antagonists. In particular, the invention discloses soluble FZD, SFRP and Ror receptors and their use.

1 - 184 . (canceled) 
     
     
         185 . An isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:50 and SEQ II) NO:53. 
     
     
         186 . The polynucleotide of  claim 185 , wherein the polypeptide further comprises an amino acid sequence selected from the group consisting of: SEQ NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. 
     
     
         187 . An isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:53. 
     
     
         188 . An isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:53 and a second amino acid sequence selected from the group consisting of: SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, and SEQ ID NO:74. 
     
     
         189 . An isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide consisting of the amino acid sequences of SEQ ID NOs:53 and 72. 
     
     
         190 . A vector comprising the polynucleotide of  claim 185 . 
     
     
         191 . A vector comprising the polynucleotide of  claim 186 . 
     
     
         192 . A vector comprising the polynucleotide of  claim 187 . 
     
     
         193 . A vector comprising the polynucleotide of  claim 188 . 
     
     
         194 . A vector comprising the polynucleotide of  claim 189 . 
     
     
         195 . An isolated cell comprising the polynucleotide of  claim 185 . 
     
     
         196 . An isolated cell comprising the polynucleotide of  claim 186 . 
     
     
         197 . An isolated cell comprising the polynucleotide of  claim 187 . 
     
     
         198 . An isolated cell comprising the polynucleotide of  claim 188 . 
     
     
         199 . An isolated cell comprising the polynucleotide of  claim 189 . 
     
     
         200 . A Wnt-binding agent produced by the cell of  claim 195 . 
     
     
         201 . A Wnt-binding agent produced by the cell of  claim 196 . 
     
     
         202 . A Wnt-binding agent produced by the cell of  claim 197 . 
     
     
         203 . A Wnt-binding agent produced by the cell of  claim 198 . 
     
     
         204 . A Wnt-binding agent produced by the cell of  claim 199 . 
     
     
         205 . A method of treating a cancer in a subject, comprising administering a therapeutically effective amount of the Wnt-binding agent of  claim 199  to the subject.