Mimetic peptides derived from collagen type IV and their use for treating angiogenesis- and lymphangiogenesis- dependent diseases
Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed. More particularly, active non-cysteine analogs (mimetics), which exhibit anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumori-genic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models are disclosed. The presently disclosed mimetic peptides also exhibit anti-lymphangiogenic and directly anti-tumorigenic properties.
1. An isolated peptide consisting of the amino acid sequence LRRFSTAPFAFININNVINF (SEQ ID NO: 17), or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising the peptide of claim 1 , and a pharmaceutically acceptable carrier.
3. A method for treating breast cancer or macular degeneration comprising administering an effective amount of the pharmaceutical composition of claim 2 .
4. The method of claim 3 , wherein the pharmaceutical composition is administered locally or systemically.
5. The method of claim 4 , wherein the pharmaceutical composition is administered parenterally.
6. The method of claim 4 , wherein the pharmaceutical composition is administered by intraocular delivery.
7. The method of claim 3 , wherein the macular degeneration is age-related macular degeneration.
8. The method of claim 3 , wherein the method treats angiogenesis in or surrounding a tumor.
9. The method of claim 8 , wherein the tumor is a primary tumor or an established metastasized tumor.
10. The method of claim 8 , wherein the method inhibits the establishment of metastasis or inhibits further metastasis of the tumor.
11. The method of claim 8 , wherein the method inhibits dissemination of tumor cells through the blood.