Methods and compositions for diagnosing and suppressing metastasis thereof

Abstract

Disclosed is a method for determining metastatic potential of tumors, a method and a composition for treating/suppressing metastasis of cancers, as well as a method for obtaining a metastasis suppressor. A particular aspect of the invention relates to a method and a composition of evaluating expression levels of connective tissue growth factor (CTGF, also known as CCN2) to determine the status of tumor invasion. Another aspect of the invention relates to a method and a composition comprising a tumor suppressor, which maintains or increases an expression level of CTGF to suppress the invasion ability of tumor cells effectively. In another aspect of the invention relates to methods for obtaining a metastasis suppressor by evaluating the expression levels of CTGF after contacting suppressor candidates with a tumor cell line system.

1 . A pharmaceutical composition for treating/suppressing metastatic tumors, comprising an effective amount of suppressor to maintain or increase the expression CTGF levels in tumor cells, and a nucleotide sequence encoding the CTGF is SEQ ID NO: 1, and wherein the tumor is at least one selected from the group consisting of lung cancer and colorectal cancer.  
     
     
         2 . The composition according to  claim 1 , wherein the tumor cells express an expression levels of CTGF which is inversely associated with the metastatic potentials.  
     
     
         3 . The composition according to  claim 1 , wherein the suppressor is CTGE.  
     
     
         4 . The composition according to  claim 1 , wherein the suppressor comprises a nucleotide sequence encoding CTGF (SEQ ID NO: 1) and a pharmaceutically acceptable carrier.  
     
     
         5 . A method for treating/suppressing metastatic tumors, comprising the steps of administrating a pharmaceutical composition to an individual suffering from a cancer, wherein the composition comprises an effective amount of tumor suppressor to maintain or increase the expression levels of CTGF, and a nucleotide encoding the CTGF is SEQ ID NO: 1, and wherein the tumor is at least one selected from the group consisting of lung cancer and colorectal cancer.  
     
     
         6 . The method according to  claim 5 , wherein the individual is a human patient.  
     
     
         7 . The method according to  claim 5 , wherein the tumor cells express an expression levels of CTGF which is inversely associated with the metastatic potentials.  
     
     
         8 . The method according to  claim 5 , wherein the cancer is lung cancer.  
     
     
         9 . The method according to  claim 5 , wherein the cancer is colorectal cancer.  
     
     
         10 . The method according to  claim 5 , wherein the suppressor is CTGE.  
     
     
         11 . The method according to  claim 5 , wherein the suppressor comprises a nucleotide sequence encoding CTGF (SEQ ID NO: 1) and a pharmaceutically acceptable carrier.  
     
     
         12 . A method for obtaining a metastasis suppressor that elevates expression levels of CTGF, comprising the steps of: 
 (1) providing at least a system with a tumor cell line;    (2) contacting tumor suppressor candidates with the system;    (3) evaluating the expression levels of CTGF;    (4) screening out the tumor suppressors that elevates expression levels of CTGF in tumor cells;    wherein the CTGF is encoded by a nucleotide of SEQ ID NO:1; and    wherein the tumor cell line is at least one selected from the group consisting of    (a) a lung cancer cell line selected from a group consisting of CL1-0, CL1-3, CL1-5, A549, H928, and NICH520;    (b) a colorectal cancer cell line selected from a group consisting of HCT 116, COLO205, HT-29, Caco-2 and CT26.