Monitoring and modulating hgf/hgfr activity

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.

1 . A method of treating a subject having lymphedema comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of hepatocyte growth factor (HGF). 
     
     
         2 . The method of  claim 1 , wherein the hepatocyte growth factor is a human hepatocyte growth factor. 
     
     
         3 . The method of  claim 1 , wherein the HGF is at least 80% identical to SEQ ID NO:1. 
     
     
         4 . The method of  claim 1 , wherein the HGF is at least 85% identical to SEQ ID NO:1. 
     
     
         5 . The method of  claim 1 , wherein the HGF is at least 90% identical to SEQ ID NO:1. 
     
     
         6 . The method of  claim 1 , wherein the HGF is at least 96% identical to SEQ ID NO:1. 
     
     
         7 . A method of treating a subject having or at risk for a neoplastic disorder, the method comprising inhibiting hepatocyte growth factor activity to thereby treat or reduce the risk of the neoplastic disorder. 
     
     
         8 . The method of  claim 7 , wherein the neoplastic disorder is a cancer. 
     
     
         9 . The method of  claim 8 , wherein the cancer is characterized by a risk of metastasis to a lymph node. 
     
     
         10 . The method of  claim 7 , wherein inhibiting hepatocyte growth factor activity comprises administering to the subject an antagonist of hepatocyte growth factor activity. 
     
     
         11 . A method of treating a subject having aged skin, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of hepatocyte growth factor (HGF). 
     
     
         12 . The method of  claim 11 , wherein the aged skin is caused by photoradiation. 
     
     
         13 . The method of  claim 11 , wherein the hepatocyte growth factor is a human hepatocyte growth factor. 
     
     
         14 . The method of  claim 11 , wherein the HGF is at least 80% identical to SEQ ID NO:1. 
     
     
         15 . The method of  claim 11 , wherein the HGF is at least 85% identical to SEQ ID NO:1. 
     
     
         16 . The method of  claim 11 , wherein the HGF is at least 90% identical to SEQ ID NO:1. 
     
     
         17 . The method of  claim 11 , wherein the HGF is at least 96% identical to SEQ ID NO:1.