Methods for detecting and inhibiting angiogenesis using antagonists

Abstract

The present invention provides methods for reducing or inhibiting angiogenesis in a tissue, by contacting α5β1 integrin in the tissue with an agent that interferes with specific binding of the α5β1 integrin to a ligand expressed in the tissue; and methods of identifying angiogenesis in a tissue, by contacting the tissue with an agent that specifically binds α5β1 integrin, and detecting specific binding of the agent to α5β1 integrin associated with a blood vessel in the tissue. Also provided are methods of diagnosing a pathological condition characterized by angiogenesis in a tissue in an individual. The invention further provides methods of reducing or inhibiting angiogenesis in a tissue in an individual, by administering to the individual an agent that interferes with the specific binding of α5β1 integrin to a ligand expressed in the tissue; and methods of reducing the severity of a pathological condition associated with angiogenesis in an individual, by administering to the individual an agent that interferes with specific binding of α5β1 integrin to a ligand in a tissue associated with the pathological condition. The invention also provides methods of identifying an agent that reduces or inhibits angiogenesis associated with α5β1 integrin expression in a tissue by contacting a tissue exhibiting angiogenesis associated with α5β1 integrin expression with an agent, and detecting a reduction or inhibition of angiogenesis in the tissue.

1 . A method of reducing or inhibiting angiogenesis in a tissue, comprising contacting α5β1 integrin in the tissue with an α5β1 integrin antagonist that interferes with specific binding of the α5β1 integrin to the ligand expressed in the tissue, thereby reducing or inhibiting angiogenesis in the tissue. 
     
     
         2 . The method of  claim 1  wherein the binding of said antagonist to said α5β1 integrin is at least two-fold greater than the binding of said antagonist to an integrin other than α5β1 integrin. 
     
     
         3 . The method of  claim 2  wherein the binding of said antagonist to said α5β1 integrin is at least five-fold greater than the binding of said antagonist to an integrin other than α5β1 integrin. 
     
     
         4 . The method of  claim 2  wherein said integrin other than α5β1 is α5β1 integrin. 
     
     
         5 . The method of  claim 1  wherein said antagonist does not interfere with the specific binding of a ligand to an integrin other than α5β1 integrin. 
     
     
         6 . The method of  claim 1  wherein the tissue is in an individual. 
     
     
         7 . The method of  claim 6  wherein the individual is a human. 
     
     
         8 . The method of  claim 1  wherein the tissue comprises a neoplasm. 
     
     
         9 . The method of  claim 8  wherein the neoplasm is a malignant neoplasm. 
     
     
         10 . The method of  claim 9  wherein the malignant neoplasm is selected from the group consisting of a sarcoma, a mesothelioma, a teratocarcinoma, an astrocytoma, and a glioblastoma. 
     
     
         11 . The method of  claim 9  wherein the malignant neoplasm is a metastatic malignant neoplasm. 
     
     
         12 . The method of  claim 9  wherein the malignant neoplasm is a carcinoma. 
     
     
         13 . The method of  claim 12  wherein the carcinoma is selected from the group consisting of a breast carcinoma, a colon carcinoma, an ovarian carcinoma, and a pancreatic carcinoma. 
     
     
         14 . The method of  claim 1  wherein the antagonist is linked to a cytotoxin. 
     
     
         15 . The method of  claim 14  wherein the cytotoxin is a cancer chemotherapeutic drug.