Peptides of Syndecan-1 For Inhibiting Angiogenesis

Abstract

The present invention provides a peptide derived from the extracellular domain of syndecan-1 that inhibits angiogenesis.

Description

[0001] The present application claims benefit of priority to U.S. Provisional Application Ser. No. 60 / 812,187, filed Jun. 9, 2006, the entire contents of which are hereby incorporated by reference.[0002] The government own rights to the present invention pursuant to funding from the National Institute of Health grant numbers R01-HD21881 and CA109010.BACKGROUND OF THE INVENTION [0003] I. Field of the Invention [0004] The present invention relates generally to the fields of protein chemistry and developmental biology. More particularly, it concerns peptide segments from the extracellular domain of syndecan-1 (Sdc-1) that can inhibit angiogenesis and can thus be used to treat angiogenesis in pathologic conditions. [0005] II. Description of Related Art [0006] A. Function of αvβ3 and αvβ5 Integrins in Angiogenesis [0007] Several different growth factors, among them fibroblast growth factor (FGF) and vascular endothelial cell growth factor (VEGF), are often released by tumors to cause end...

AI Technical Summary

Benefits of technology

[0023] In a further embodiment, there is provided a method of inhibiting interaction of αvβ3 or αvβ5 integrin with syndecan-1 comprising contacting a αvβ3 or αvβ5 integrin molecule with a peptide or polypeptide segment consisting of between 5 and 100 amino acid residues or less residues and comprising SEQ ID NO:21 or SEQ ID NO:13. The peptide or polypeptide may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 amino acid residues in length, or any range derivable therein. In certain embodiments, the peptide does not have an amino acid sequence that consists of SEQ ID NO:28. The peptide may consist of SEQ ID NO:10. In other embodiments, the peptide may consist of or comprise SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:23, or SEQ ID NO:28. The αvβ3 or αvβ5 integrin may be located on the surface of a cell, such as a cancer cell (e.g., a carcinoma, a myeloma, a melanoma or a glioma), including a metastatic cancer cell. The method may further comprise contacting said cancer cell with a second cancer inhibitory agent.

[0024] In yet a further embodiment, there is provided a method of inhibiting αvβ3 or αvβ5 integrin activation by syndecan-1 comprising contacting a cell expressing an αvβ3 or αvβ5 integrin molecule with a peptide or polypeptide segment consisting of between 5 and 100 amino acid residues and comprising SEQ ID NO:21 or SEQ ID NO:13. In certain embodiments, the peptide does not have an amino acid sequence that consists of SEQ ID NO:28. The peptide or polypeptide may be 10, 15, 20, 25, 30, 35, 40, 45, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 amino acid residues in length. The peptide may consist of SEQ ID NO:10. In other embodiments, the peptide may consist of or comprise SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:23, or SEQ ID NO:28. The inhibiting may result in inhibition of cell adhesion, migration, cell metastasis, cell survival and/or cell proliferation.

[0025] In still yet a further embodiment, there is provided a method of treating a subject with a cancer, cells of which express αvβ3 or αvβ5 integrin, comprising contacting said cells with a peptide or polypeptide segment consisting of between 5 and 100 amino acid residues or less residues and comprising SEQ ID NO:21 or SEQ ID NO:13. In certain embodiments, the peptide does not have an amino acid sequence that consists of SEQ ID NO:28. The peptide or polypeptide may be 10, 15, 20, 25, 30, 35, 40, 45, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 amino acid residues in length. The peptide may consist of SEQ ID NO:10. In other embodiments, the peptide may consist or comprise SEQ ID NO:1, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:23, or SEQ ID NO:28. The subject may be a human. The cancer may be a carcinoma, a myeloma, a melanoma or a glioma. The peptide or polypeptide may be administered directly to said cance

Problems solved by technology

Although endothelial cells in mature vessels are not readily susceptible to apoptosis, angiogenic cells that are induced by growth factors are highly susceptible and rely upon the continued presence of these factors for survival.

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