MT-SP1 polypeptides

Abstract

This invention provides a novel membrane-type serine protease (designated MT-SP1) elevated expression of which is associated with cancer. In one embodiment, this invention provides a method obtaining a prognosis or of detecting or staging a cancer in an organism. The method involves providing a biological sample from the organism and detecting the level of a membrane type serine protease 1 (MT-SP1) in the sample, where an elevated level of the membrane-type serine protease, as compared to the level of the protease in a biological sample from a normal healthy organism indicates the presence or stage of the cancer.

1 - 80 . (canceled)  
     
     
         81 . An isolated polypeptide consisting of a serine proteinase domain that is at least 95% identical to the amino acid sequence from residue 615 to 855 shown in SEQ ID NO. 2 and optionally a fusion protein thereto, wherein said domain exhibits serine proteinase activity.  
     
     
         82 . The isolated polypeptide of  claim 81 , wherein the MT-SP1 serine protease domain exhibits specific protease activity towards a target substrate.  
     
     
         83 . The isolated polypeptide of  claim 81 , wherein said MT-SP1 serine protease domain has the sequence of amino acids 615 through 855 of SEQ ID NO:2.  
     
     
         84 . The polypeptide of  claim 81 , wherein the target substrate has the formula of Suc-AAPX-pNA, wherein: 
 Suc is N-succinyl,    A is alanyl,    P is prolyl    pNA is paranitroanaline acetate    X is selected from the group consisting of alanyl, aspartyl, glutamyl, phenylalanyl, leucinyl, methionyl, and arginyl residue.    
     
     
         85 . The polypeptide of  claim 84  having a k cat  of about 2.6×10 2 /second or greater in a protease reaction utilizing Spectozyme tPA as the target substrate.  
     
     
         86 . The polypeptide of  claim 84  having the sequence of amino acids 615 through 855 of SEQ ID NO:2.  
     
     
         87 . An isolated polypeptide comprising an isolated MT-SP1 serine proteinase domain that is substantially free of MT-SP1 sequences from domains other than the serine proteinase domain.  
     
     
         88 . The isolated polypeptide of  claim 87 , wherein the isolated MT-SP1 serine proteinase domain comprises C-terminal sequence of MT-SP1 having a length less than about 250 amino acids.  
     
     
         89 . The isolated polypeptide of  claim 87  that exhibits serine proteinase activity.  
     
     
         90 . The isolated polypeptide of  claim 87  that substantially lacks serine proteinase activity.  
     
     
         91 . The isolated polypeptide of  claim 81 , wherein the fusion protein comprises an epitope tag.  
     
     
         92 . The isolated polypeptide of  claim 81  that is labeled with a detectable label.  
     
     
         93 . The isolated polypeptide of  claim 87  that is labeled with a detectable label.  
     
     
         94 . The isolated polypeptide of  claim 81  that is bound to an anti-MT-SP1 antibody.  
     
     
         95 . The isolated polypeptide of  claim 87  that is bound to an anti-MT-SP1 antibody.