Methods of using the FRI domain of human frizzled receptor for inhibiting Wnt signaling in a tumor or tumor cell
The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.
1. A method of inhibiting Wnt signaling in a tumor or tumor cell, comprising contacting the tumor or tumor cell with an effective amount of a soluble receptor, wherein the soluble receptor comprises a polypeptide consisting of:
(a) a fragment of an extracellular domain of a human Frizzled receptor, wherein the fragment consists essentially of the Fri domain of the human FZD receptor, and the human FZD receptor is FZD4, FZD5, or FZD8; and
(b) a non-FZD receptor protein sequence comprising:
(i) a human Fc domain; or
(ii) a polypeptide having the amino acid sequence of SEQ ID NO:4.
2. The method of claim 1 , wherein the fragment comprises the amino acids from approximately 28 to 158 of SEQ NO:7, the amino acids from approximately 37 to 170 of SEQ ID NO:8, or the amino acids from approximately 27 to 157 of SEQ ID NO:9.
3. The method of claim 1 , wherein the fragment consists of the amino acids 28 to 158 of SEQ ID NO:7, the amino acids 37 to 170 of SEQ ID NO:8, or the amino acids 27 to 157 of SEQ ID NO:9.
4. The method of claim 1 , wherein the non-FZD receptor protein sequence comprises a human Fc domain.
5. The method of claim 1 , wherein the non-FZD receptor protein sequence comprises a polypeptide having the amino acid sequence of SEQ ID NO:4.
6. The method of claim 1 , wherein the fragment consists essentially of the Fri domain of human FZD8.
7. The method of claim 6 , wherein the Fri domain of human FZD8 comprises the amino acids from approximately 28 to 158 of the amino acid sequence of SEQ ID NO:7.
8. The method of claim 1 , wherein the fragment consists essentially of the Fri domain of human FZD4.
9. The method of claim 8 , wherein the Fri domain of human FZD4 comprises the amino acids from approximately 37 to 170 of the amino acid sequence of SEQ ID NO:8.
10. The method of claim 1 , wherein the fragment consists essentially of the Fri domain of human FZD5.
11. The method of claim 10 , wherein the Fri domain of human FZD5 comprises the amino acids from approximately 27 to 157 of the amino acid sequence of SEQ ID NO:9.
12. The method of claim 1 , wherein the tumor or tumor cells are from a breast tumor, colorectal tumor, lung tumor, pancreatic tumor, prostate tumor, or a head and neck tumor.