Monitoring and Modulating HGF/HGFR Activity
AssigneeThe General Hospital Corporation
InventorsMichael Detmar, Kentaro Kajiya
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Abstract
Provided are methods and compositions for the modulation of hepatocyte growth factor activity to regulate lymphatic vessel development and function. Methods and composition for the monitoring and treatment of skin disorders, lymphedema, and metastatic cancers are disclosed. Also described are methods of identifying inhibitors of hepatocyte growth factor dependent lymphangiogenesis.
Claims35
A method of treating a subject having an unwanted skin condition comprising increasing hepatocyte growth factor activity to thereby treat the disorder.
A method of treating a subject having lymphedema comprising increasing hepatocyte growth factor activity to thereby treat the lymphedema.
A method of treating a subject having or at risk for a neoplastic disorder comprising inhibiting hepatocyte growth factor activity to thereby treat or reduce the risk of the neoplastic disorder.
A method of treating a subject having or at risk for a neoplastic disorder comprising inhibiting α9 integrin activity to thereby treat or reduce the risk of the neoplastic disorder.
A method of identifying a compound that inhibits hepatocyte growth factor-dependent lymphatic endothelial cell proliferation or migration, comprising:
- providing a lymphatic endothelial cell expressing the hepatocyte growth factor receptor;
- contacting the lymphatic endothelial cell with hepatocyte growth factor and a test compound;
- and
- determining whether proliferation of the lymphatic endothelial cell is decreased in the presence of the test compound, a decrease in the proliferation being an indication that the test compound inhibits hepatocyte growth factor-dependent lymphatic endothelial cell proliferation.
A method of identifying a compound that inhibits hepatocyte growth factor-dependent lymphangiogenesis comprising:
- providing lymphatic endothelial cells expressing the hepatocyte growth factor receptor;
- contacting the lymphatic endothelial cells with hepatocyte growth factor and a test compound;
- and
- determining if lymphangiogenesis is decreased, wherein a decrease in lymphangiogenesis is an indication that the compound inhibits hepatocyte growth factor-dependent lymphangiogenesis.
Dependencies are inferred from the claim text.