Bone morphogenetic protein-2 in the treatment and diagnosis of cancer

Abstract

The present invention pertains to the use of BMP-2, which is overexpressed in most common cancers, as 1) a target for cancer treatment therapies and 2) a means to diagnose cancer. The therapeutic component of this invention involves administering to a patient a composition that inhibits bone morphogenetic-2 activity. Such inhibition may be accomplished by ligands or antibodies that bind to BMP-2 or BMP-2 receptors. It may also be achieved by preventing the processing of pro-BMP-2, or blocking transcription or replication of BMP-2 DNA or translation of BMP-2 mRNA. The diagnostic component of the invention involves measuring the BMP-2 level in biological samples from both a patient and a subject and comparing those levels. Elevated levels of BMP-2 in the patient compared to the non-cancerous subject indicate cancer.

I claim:  
     
         1 . A method of reducing vascularization of a tumor in a subject comprising administering to the subject a therapeutically effective amount of a bone morphogenetic protein-2 (BMP-2) activity inhibitor.  
     
     
         2 . The method of  claim 1 , wherein the tumor is a thoracic tumor.  
     
     
         3 . The method of  claim 1 , wherein the tumor is a cancerous tumor.  
     
     
         4 . The method of  claim 3 , wherein the cancerous tumor is carcinoma.  
     
     
         5 . The method of  claim 4 , wherein the carcinoma is selected from the group consisting of bladder cancer, breast cancer, colon cancer, kidney cancer, lung cancer, ovarian cancer, thyroid cancer, endometrial cancer, omental cancer, testicular cancer, and liver cancer.  
     
     
         6 . The method of  claim 4 , wherein the carcinoma is a lung cancer.  
     
     
         7 . The method of  claim 1 , wherein reducing vascularization comprises inhibiting neoangiogenesis.  
     
     
         8 . The method of  claim 1 , wherein reducing vascularization comprises inhibiting the growth or development of existing vasculature.  
     
     
         9 . The method of  claim 1 , wherein the BMP-2 activity inhibitor is a polypeptide that binds specifically to BMP-2 or to a BMP-2 receptor.  
     
     
         10 . The method of  claim 1 , wherein the BMP-2 activity inhibitor is selected from the group consisting of noggin, chordin, cerberus 1 homolog, gremlin, and an antibody to BMP-2.  
     
     
         11 . The method of  claim 10 , wherein the BMP-2 activity inhibitor is noggin.  
     
     
         12 . The method of  claim 11 , wherein the amino acid sequence of noggin is selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 6.  
     
     
         13 . The method of  claim 1 , wherein the BMP-2 activity inhibitor is an antisense oligonucleotide that binds to a BMP-2 nucleic acid sequence.  
     
     
         14 . The method of  claim 1 , wherein the BMP-2 activity inhibitor is administered in a pharmaceutically acceptable carrier.  
     
     
         15 . The method of  claim 1 , wherein the BMP-2 activity inhibitor is administered orally, enterically, intravenously, peritoneally, subcutaneously, transdermally, parenterally, intratumorally, or rectally.  
     
     
         16 . A method of reducing vascularization of a tumor in a subject comprising administering to the subject a therapeutically effective amount of an expression vector having a nucleic acid sequence encoding a BMP-2 activity inhibitor and a selective promoter that is operably linked to the nucleic acid sequence.  
     
     
         17 . The method of  claim 16 , wherein the tumor is lung cancer.  
     
     
         18 . The method of  claim 16 , wherein the expression vector is administered in a pharmaceutically acceptable carrier.  
     
     
         19 . The method of  claim 16 , wherein the expression vector is administered orally, enterically, intravenously, peritoneally, subcutaneously, transdermally, parenterally, intratumorally, or rectally.  
     
     
         20 . The method of  claim 16 , wherein reducing vascularization comprises inhibiting neoangiogenesis or inhibiting the growth or development of existing vasculature.