Pharmaceutical compositions and methods useful for modulating angiogenesis and inhibiting metastasis and tumor fibrosis

Abstract

Methods and compositions suitable for modulating angiogenesis in a mammalian tissue are provided. Further provided are methods suitable for inhibiting metastasis and fibrosis in a mammalian tissue.

What is claimed is:  
     
         1 . A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a molecule capable of modifying a tissue level and/or activity of at least one type of lysyl-oxidase to thereby modulate angiogenesis in the mammalian tissue.  
     
     
         2 . The method of  claim 1 , wherein said molecule is an antibody or an antibody fragment capable of binding with, and at least partially inhibiting said activity of, said at least one polypeptide.  
     
     
         3 . The method of  claim 2 , wherein said antibody or said antibody fragment is directed against at least an antigenic portion of the polypeptide set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         4 . The method of  claim 1 , wherein said molecule is a polynucleotide capable of downregulating expression of said at least one type of lysyl-oxidase.  
     
     
         5 . The method of  claim 4 , wherein said polynucleotide is at least partially complementary with the polynucleotide set forth in SEQ ID NO: 1, 4, 5 or 7.  
     
     
         6 . The method of  claim 1 , wherein said molecule is a polypeptide having lysyl-oxidase activity.  
     
     
         7 . The method of  claim 6 , wherein said polypeptide is as set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         8 . A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a nucleic acid construct being capable of expressing a polypeptide having lysyl-oxidase activity to thereby modulate angiogenesis within the mammalian tissue.  
     
     
         9 . The method of  claim 8 , wherein said polypeptide is at least 75% homologous to the polypeptide set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         10 . A method of identifying molecules capable of modulating angiogenesis, the method comprising: 
 (a) isolating molecules which exhibit specific reactivity with at least one type of lysyl-oxidase; and    (b) testing said molecules within mammalian tissue so as to determine the angiogenesis modulation activity thereof.    
     
     
         11 . The method of  claim 10 , wherein step (a) is effected by binding assays and/or lysyl-oxidase activity assays.  
     
     
         12 . A pharmaceutical composition useful for modulating angiogenesis in mammalian tissue, the composition-of matter comprising, as an active ingredient, a molecule capable of modifying a level and/or activity of at least one type of lysyl-oxidase of the mammalian tissue and a pharmaceutically effective carrier.  
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein said molecule is an antibody or an antibody fragment capable of binding with, and at least partially inhibiting said activity of, said at least one type of lysyl-oxidase.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein said antibody or said antibody fragment is directed against at least a portion of the polypeptide set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein said molecule is a polynucleotide capable of downregulating expression of said at least one type of lysyl-oxidase.  
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein said polynucleotide is at least partially complementary with the polynucleotide set forth in SEQ ID NO: 1, 4, 5 or 7.  
     
     
         17 . The pharmaceutical composition of  claim 12 , wherein said molecule is a polypeptide having lysyl-oxidase activity.  
     
     
         18 . The pharmaceutical composition of  claim 12 , wherein said polypeptide is as set forth SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         19 . A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a molecule capable of modifying a tissue level and/or a lysyl-oxidase activity of a polypeptide at least 75% homologous to the polypeptide set forth in SEQ ID NO: 2 to thereby modulate angiogenesis in the mammalian tissue.  
     
     
         20 . A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a nucleic acid construct being capable of expressing a polypeptide at least 75% homologous to the polypeptide set forth in SEQ ID NO: 2 to thereby modulate angiogenesis within the mammalian tissue.  
     
     
         21 . A method of determining the malignancy of cancerous tissue, the method comprising 
 (a) determining a lysyl-oxidase expression level and/or activity of the cancerous tissue; and    (b) comparing said lysyl-oxidase expression level and/or activity with that determined for control tissue to thereby determine the malignancy of the cancerous tissue.    
     
     
         22 . A method of inhibiting metastasis and/or fibrosis in a mammalian tissue, the method comprising administering to the mammalian tissue a molecule capable of downregulating a tissue level and/or activity of at least one type of lysyl-oxidase to thereby inhibit metastasis in the mammalian tissue.  
     
     
         23 . The method of  claim 22 , wherein said molecule is an antibody or an antibody fragment capable of specifically binding with said at least one type of lysyl-oxidase.  
     
     
         24 . The method of  claim 22 , wherein said antibody or said antibody fragment is directed against at least an antigenic portion of the polypeptide set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         25 . The method of  claim 22 , wherein said molecule is a polynucleotide capable of downregulating expression of said at least one type of lysyl-oxidase.  
     
     
         26 . The method of  claim 25 , wherein said polynucleotide is at least partially complementary with the polynucleotide set forth in SEQ ID NO: 1, 4, 5 or 7.  
     
     
         27 . A method of identifying molecules capable of inhibiting metastasis and/or fibrosis, the method comprising: 
 (a) screening and identifying molecules which exhibit specific reactivity with at least one type of lysyl-oxidase; and    (b) testing a metastasis and/or fibrosis inhibitory potential of said molecules.    
     
     
         28 . The method of  claim 27 , wherein step (a) is effected by binding assays and/or lysyl-oxidase activity assays.  
     
     
         29 . The method of  claim 27 , wherein step (b) is effected in-vivo or in-vitro.  
     
     
         30 . A pharmaceutical composition useful for inhibiting metastasis and/or fibrosis in mammalian tissue, comprising, as an active ingredient, a molecule capable of downregulating a level and/or activity of at least one type of lysyl-oxidase present within the mammalian tissue and a pharmaceutically effective carrier.  
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein said molecule is an antibody or an antibody fragment capable of specifically binding with said at least one type of lysyl-oxidase.  
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein said antibody or said antibody fragment is directed against at least an antigenic portion of the polypeptide set forth in SEQ ID NO: 2, 3, 6, 8 or 9.  
     
     
         33 . The pharmaceutical composition of  claim 30 , wherein said molecule is a polynucleotide capable of downregulating expression of said at least one type of lysyl-oxidase.  
     
     
         34 . The pharmaceutical composition of  claim 33 , wherein said polynucleotide is at least partially complementary with the polynucleotide set forth in SEQ ID NO: 1, 4, 5 or 7.  
     
     
         35 . A method of inhibiting metastasis and fibrosis in a mammalian tissue, the method comprising administering to the mammalian tissue a molecule capable of downregulating a tissue level and/or a lysyl-oxidase activity of a polypeptide at least 75% homologous to the polypeptide set forth in ID NO: 2 or 9, to thereby inhibit metastasis and fibrosis in the mammalian tissue.