Syndecan peptides and polypeptides as inhibitors of cancer
The invention provides for peptides from syndecan 1 and methods of use therefor. These peptides can inhibit α4β6 interaction with HER2, thereby preventing tumor cell growth and tissue invasion.
1. A method of inhibiting α6β4 integrin interaction with HER2/Neu on the surface of a cancer cell comprising administering to said subject a peptide segment consisting of between 26 and 100 amino acid residues and comprising 210-235 of SEQ ID NO:1 such that the surface of said cancer cell is contacted by said peptide.
2. The method of claim 1 , wherein said cancer cell is a carcinoma, a melanoma, a schwannoma, a malignant peripheral nerve sheath tumor cell or a glioma.
3. A method of treating a subject with a cancer, cancer cells of which express α6β4 integrin and HER2/Neu, comprising administering to said subject a peptide segment consisting of between 26 and 100 amino acid residues and comprising residues 210-235 of SEQ ID NO:1 such that said cancer cells are contacted by said peptide.
4. The method of claim 3 , wherein said cancer is a carcinoma, a melanoma or a glioma.
5. The method of claim 1 , wherein said peptide or polypeptide is 27, 28, 29, 30, 31, 32, 33, 34, 35, 40, 45, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 amino acid residues in length.
6. The method of claim 1 , wherein said peptide is between 31 and 80 amino acid residues in length.
7. The method of claim 1 , wherein said peptide is between 61 and 80 amino acid residues in length.
8. The method of claim 1 , wherein said peptide is between 66 and 80 amino acid residues in length.
9. The method of claim 1 , wherein said peptide consists essentially of residues 210-235 (SEQ ID NO: 2) or residues 210-240 (SEQ ID NO 3).
10. The method of claim 1 , wherein said peptide comprises residues 210-240 (SEQ ID NO: 3).
11. The method of claim 1 , wherein said peptide consists essentially of residues 210-240 (SEQ ID NO: 3), 210-249 (SEQ ID NO: 4), 175-235 (SEQ ID NO: 5) or 175-240 (SEQ ID NO: 6).
12. The method of claim 1 , wherein said peptide consists of residues 210-240 (SEQ ID NO: 3), 210-249 (SEQ ID NO: 4), 175-235 (SEQ ID NO: 5) or 175-240 (SEQ ID NO: 6).
13. The method of claim 1 , further comprising contacting said cancer cell with a second cancer inhibitory agent.
14. The method of claim 1 , wherein said cancer cell is a metastatic cancer cell or tumor stem cell.
15. The method of claim 1 , wherein contacting comprises providing to said cell an expression construct comprising a nucleic acid encoding a peptide segment consisting of between 31 and 100 amino acid residues and comprising residues 210-240 of SEQ ID NO:1 operably linked to a promoter active in said cell.
16. The method of claim 1 , wherein said peptide consists of residues 210-235 (SEQ ID NO: 2).
17. The method of claim 1 , wherein said peptide consists of residues 210-240 (SEQ ID NO: 3).
18. The method of claim 3 , wherein said peptide consists of residues 210-235 (SEQ ID NO: 2).
19. The method of claim 3 , wherein said peptide consists of residues 210-240 (SEQ ID NO: 3).
20. The method of claim 3 , wherein said peptide consists essentially of residues 210-240 (SEQ ID NO: 3), 210-249 (SEQ ID NO: 4), 175-235 (SEQ ID NO: 5) or 175-240 (SEQ ID NO: 6).