Compositions and methods for treating neoplastic disease using inhibitors of laminin5beta3

Abstract

Inhibitors of laminin5beta3 are provided that reduce the expression or biological activities of laminin5beta3 or the expression of laminin5beta3 mRNA in a mammalian cell. Laminin5beta3 inhibitors include antisense molecules, ribozymes, antibodies and antibody fragments, proteins and polypeptides as well as small molecules. Laminin5beta3 inhibitors find use in compositions and methods for decreasing laminin5beta3 gene expression as well as methods for inhibiting the proliferation of mammalian cells, including tumor cells of epithelial origin, and methods for treating neoplastic diseases.

What is claimed is:  
     
         1 . An isolated laminin5beta3 inhibitor selected from the group consisting of an antisense oligonucleotide, a ribozyme, a protein, a polypeptide, an antibody, and a small molecule.  
     
     
         2 . The isolated laminin5beta3 inhibitor of  claim 1  wherein said laminin5beta3 inhibitor is an antisense molecule.  
     
     
         3 . The isolated laminin5beta3 inhibitor of  claim 2  wherein said antisense molecule or the complement thereof comprises at least 15 consecutive nucleic acids of the sequence of SEQ ID NO:1.  
     
     
         4 . The isolated laminin5beta3 inhibitor of  claim 3  wherein said antisense molecule or the complement thereof hybridizes under high stringency conditions to the sequence of SEQ ID NO:1.  
     
     
         5 . The isolated laminin5beta3 inhibitor of  claim 2  wherein said antisense molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:2 and 3.  
     
     
         6 . A composition, comprising a therapeutically effective amount of a laminin5beta3 inhibitor in a pharmaceutically acceptable carrier.  
     
     
         7 . The composition of  claim 6 , comprising two or more laminin5beta3 inhibitors.  
     
     
         8 . The composition of  claim 6  wherein said laminin5beta3 inhibitor is an antisense molecule.  
     
     
         9 . The composition of  claim 8  wherein said antisense molecule or the complement thereof comprises at least 15 consecutive nucleic acids of the sequence of SEQ ID NO:1.  
     
     
         10 . The composition of  claim 9  wherein said antisense molecule or the complement thereof hybridizes under high stringency conditions to the sequence of SEQ ID NO:1.  
     
     
         11 . The composition of  claim 6  wherein said antisense molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:2 and 3.  
     
     
         12 . A method of decreasing the expression of laminin5beta3 in a mammalian cell, comprising administering to said cell a laminin5beta3 inhibitor of  claim 1 .  
     
     
         13 . The method of  claim 12  wherein said laminin5beta3 inhibitor is an antisense molecule.  
     
     
         14 . The method of  claim 13  wherein said antisense molecule or the complement thereof comprises at least 15 consecutive nucleic acids of the sequence of SEQ ID NO:1.  
     
     
         15 . The method of  claim 13  wherein said antisense molecule or the complement thereof hybridizes under high stringency conditions to the sequence of SEQ ID NO: 1.  
     
     
         16 . The method of  claim 13  wherein said antisense molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:2 and 3.  
     
     
         17 . A method of treating neoplastic disease, comprising administering to a mammalian cell a laminin5beta3 inhibitor of  claim 1  such that said neoplastic disease is reduced in severity.  
     
     
         18 . The method of  claim 17  wherein said neoplastic disease is of epithelial origin.  
     
     
         19 . The method of  claim 18  wherein said disease is selected from the group consisting of colon, breast, and prostate cancer.  
     
     
         20 . A diagnostic kit for detecting the presence of a tumor cell of epithelial origin in a biological sample, said kit comprising at least one oligonucleotide selected from the group consisting of SEQ ID NOs:2 and 3, and at least one control oligonucleotide that does not hybridize with a polynucleotide of SEQ ID NO:1 under stringent conditions.  
     
     
         21 . The kit of  claim 20  comprising oligonucleotides of SEQ ID NO:2 and 3.  
     
     
         22 . The kit of  claim 20  wherein said tumor cell is of colon origin.  
     
     
         23 . The kit of  claim 20  wherein said tumor cell is of prostate origin.