Inhibin as targetable regulators of angiogenesis

Abstract

Contact of endothelial cells with inhibitors of inhibin and/or the alpha-subunit of inhibin can be utilized to modify the activity of endothelial cell expression products including SMAD1/5. Methods can also include inhibiting ALK1 and/or endoglin as components of inhibin-activated pathway of SMAD1/5 signaling. Methods can be combined with other anti-angiogenesis therapies such as anti-VEGF therapies. Methods can be utilized in treatment of inhibin-expressing cancers (e.g., ovarian cancer, pancreatic cancer) as well as other pathologies such as pre-eclampsia and PCOS.

What is claimed is: 
     
         1 . A method comprising delivering a composition comprising an anti-α-inhibin antibody to an environment that includes an endothelial cell and the alpha-subunit of inhibin. 
     
     
         2 . The method of  claim 1 , wherein the alpha-subunit of inhibin is linked with a beta-subunit of inhibin and in the form of a heterodimer inhibin. 
     
     
         3 . The method of  claim 1 , wherein the alpha-subunit of inhibin has been expressed from a cancer cell. 
     
     
         4 . The method of  claim 3 , wherein the cancer cell is an ovarian cancer cell. 
     
     
         5 . The method of  claim 3 , wherein the ovarian cancer cell is an endometrial cancer cell, a serous cancer cell, or a mucinous cancer cell. 
     
     
         6 . The method of  claim 3 , wherein the cancer cell is a prostate cancer cell, a renal cancer cell, a lung cancer cell, a gastric cancer cell, or a breast cancer cell. 
     
     
         7 . The method of  claim 3 , the environment further comprising the cancer cell. 
     
     
         8 . The method of  claim 1 , further comprising delivering to the environment an antibody that specifically binds an activin receptor-like kinase. 
     
     
         9 . The method of  claim 1 , further comprising delivering to the environment an antibody that specifically binds endoglin. 
     
     
         12 . The method of  claim 1 , further comprising delivering an anti-VEGF therapy to the area. 
     
     
         13 . The method of  claim 1 , wherein the environment is an in vivo environment. 
     
     
         14 . A composition comprising:
 a biologically acceptable carrier;   an anti-α-antibody; and   at least one of an anti-activin receptor-like kinase 1 antibody and an anti-endoglin antibody.   
     
     
         15 . The composition of  claim 14 , the composition comprising the anti-α-antibody in a concentration of from about 0.0001 μM to about 0.5 M. 
     
     
         16 . The composition of  claim 14 , the composition comprising the at least one of an anti-activin receptor-like kinase 1 antibody and an anti-endoglin antibody in a concentration of from about 0.0001 μM to about 0.5 M. 
     
     
         17 . The composition of  claim 14 , the composition comprising both the anti-activin receptor-like kinase 1 antibody and an anti-endoglin antibody. 
     
     
         18 . The composition of  claim 14 , the composition further comprising an anti-VEGF.