Treatment of metastatic colon cancer with b-subunit of shiga toxin

Abstract

The present invention relates to compositions and methods for treating invasive or metastatic cancer, particularly metastatic colon cancer using the B-submit of shiga toxin. The invention further provides methods of identifying compounds usefully for the treatment of invasive or metastatic cancer, particularly metastatic colon cancer.

1 . A method of preventing, reducing, or inhibiting invasiveness and metastasis of tumor cells in a subject comprising administering to the subject a therapeutically effective amount of the B-subunit of Shiga toxin. 
     
     
         2 . The method of  claim 1 , wherein the tumor cells are colon tumor cells. 
     
     
         3 . The method of  claim 1 , wherein the tumor cells are derived from a tissue selected from the group consisting of: colon, lung, brain, skin, ovary, pancreas, liver, stomach, bladder, bone, testicle, uterus, adipose tissue, throat, kidney, tongue, pituitary gland, thyroid, lymphoid tissue, eye, and cervix. 
     
     
         4 . The method of  claim 1 , wherein the B-subunit of Shiga toxin is Stx1 B. 
     
     
         5 . The method of  claim 1 , wherein the B-subunit of Shiga toxin is Stx2B. 
     
     
         6 . The method of  claim 1 , wherein the therapeutically effective amount of the B-subunit of Shiga toxin of is administered prior to the onset of metastasis by the tumor cells. 
     
     
         7 . The method of  claim 1 , wherein the therapeutically effective amount of the B-subunit of Shiga toxin is administered subsequent to the onset of metastasis by the tumor cells. 
     
     
         8 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of radiation. 
     
     
         9 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of at least one chemotherapeutic agent. 
     
     
         10 . The method of  claim 1 , wherein the tumor cells produce Gb 3 . 
     
     
         11 . The method of  claim 1 , wherein the subject is a human. 
     
     
         12 . The method of  claim 1 , wherein the B subunit of Shiga toxin is conjugated to a therapeutic moiety. 
     
     
         13 . A method of identifying a compound capable of preventing, reducing, or inhibiting tumor cell invasiveness and metastasis comprising:
 a) contacting a cell that produces Gb 3  with a test compound; and   b) measuring Gb 3  production or activity by the cell,   wherein a compound which reduces or inhibits Gb 3  production by the tumor cells is identified as a compound capable of preventing, reducing, or inhibiting tumor cell metastasis.   
     
     
         14 . The method of  claim 13 , wherein measuring Gb 3  production comprises measuring the level Gb 3  Synthetase mRNA. 
     
     
         15 . The method of  claim 14 , wherein the Gb 3  Synthetase mRNA level is measured using a method selected from the group consisting of: Northern blotting, RNAse protection, primer extension, and RT-PCR. 
     
     
         16 . The method of  claim 13 , wherein measuring Gb 3  expression comprises measuring the level Gb 3  lipid. 
     
     
         17 . The method of  claim 16 , wherein the Gb 3  lipid level is measured using a method selected from the group consisting of: chromatography, ELISA, RIA, FACS, and immunocytochemistry.