Sequences for targeting metastatic cells

Abstract

The present invention relates to methods for the diagnosis, evaluation and treatment of metastatic diseases using metastatic sequences, such as caveolin, to target metastatic cells. According to the methods of the present invention, certain cancers, including metastatic prostate cancer, may be treated by therapies which suppress expression of the caveolin gene. The present invention relates to biological technologies designed to block the activity of caveolin or the function of caveolae, including vector delivery of antisense caveolin sequences, the use of anti-caveolin antibodies, the use of promoters, and other approaches targeting the expression of caveolin.

I claim:  
     
         1 . A method for treating a patient having a metastatic tumor comprising delivering a therapeutically effective amount of an antisense caveolin nucleic acid to said patient.  
     
     
         2 . The method of  claim 1  wherein the nucleic acid comprises RNA, DNA or PNA.  
     
     
         3 . The method of  claim 1  wherein the nucleic acid is expresses from a viral vector.  
     
     
         4 . The method of  claim 3  wherein the viral vector is a vaccinia virus vector, a retrovirus vector, an adenovirus vector or a combination thereof.  
     
     
         5 . The method of  claim 1  wherein the nucleic acid encodes an antisense sequence of the entire caveolin-1 gene.  
     
     
         6 . The method of  claim 1  wherein the nucleic acid encodes an antisense sequence of an effective portion of the caveolin-1 gene.  
     
     
         7 . The method of  claim 6  wherein the effective portion encodes the scaffolding domain or the dimerization domain of caveolin-1.  
     
     
         8 . The method of  claim 6  wherein the effective portion comprises the transcription promoter of the caveolin-1 gene.  
     
     
         9 . The method of  claim 8  wherein the promoter is functionally coupled to a gene which encodes an anti-metastatic therapeutic agent.  
     
     
         10 . A method for treating a metastatic disorder comprising administering to a patient having said disorder an effective amount of an anti-caveolin antibody.  
     
     
         11 . The method of  claim 10  wherein the metastatic disorder is metastatic prostate or breast cancer.  
     
     
         12 . The method of  claim 10  wherein the antibody is reactive against the scaffolding domain or the dimerization domain of a caveolin protein.  
     
     
         13 . A method for evaluating the metastatic potential of a primary prostate tumor comprising: 
 contacting a sample of the tumor with an anti-caveolin antibody coupled to a detectable marker; and    determining the amount of antibody bound to the sample.    
     
     
         14 . The method of  claim 13  wherein the anti-caveolin antibody is coupled to a detectable label.  
     
     
         15 . The method of  claim 13  wherein the anti-caveolin anibody is a monoclonal or a polyclonal antibody.  
     
     
         16 . A method for treating a patient for prostate cancer comprising the steps of: 
 suppressing caveolin expression by the prostate cancer; and    reducing the level of androgen in the patient.    
     
     
         17 . The method of  claim 16  wherein the caveolin expression is suppressed by administering an anti-sense caveolin nucleic acid to the patient.  
     
     
         18 . The method of  claim 16  wherein the level of androgen is reduced by administering anti-androgen therapy to the patient.  
     
     
         19 . An isolated promoter that is specific for expression in metastatic cells.  
     
     
         20 . The promoter of  claim 19  which is a caveolin promoter.  
     
     
         21 . The promoter of  claim 19  further comprising a gene which encodes an anti-metastatic therapeutic agent.  
     
     
         22 . The promoter of  claim 21  wherein the therapeutic agent is a toxin.  
     
     
         23 . The promoter of  claim 22  wherein the toxin is an apoptotic inducer.  
     
     
         24 . The promoter of  claim 21  wherein the therapeutic agent is a cytokine.  
     
     
         25 . The promoter of  claim 24  wherein the cytokine is IL-2.