Method for inhibiting tumor invasion or spreading in a subject

Abstract

The present invention provides for a method for inhibiting tumor invasion or metastasis in a subject which comprises administering to the subject a therapeutically effective amount of a form of soluble Receptor for Advanced Glycation Endproducts (RAGE). The present invention also provides a method for evaluating the ability of an agent to inhibit tumor invasion in a local cellular environment which comprises: (a) admixing with cell culture media an effective amount of the agent; (b) contacting a tumor cell in cell culture with the media from step (a); (c) determining the amount of spreading of the tumor cell culture, and (d) comparing the amount of spreading of the tumor cell culture determined in step (c) with the amount determined in the absence of the agent, thus evaluating the ability of the agent to inhibit tumor invasion in the local cellular environment. The present invention also provides a pharmaceutical composition which comprises a therapeutically effective amount of the agent evaluated in the aforementioned method and a pharmaceutically acceptable carrier.

1 . A method for inhibiting tumor invasion or metastasis in a subject which comprises administering to the subject a therapeutically effective amount of an agent which comprises a V domain of soluble Receptor for Advanced Glycation Endproduct (RAGE). 
     
     
         2 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , further comprising administering a pharmaceutically acceptable carrier to the subject during the administration of the form of soluble RAGE. 
     
     
         9 . The method of  claim 1 , wherein the administration is via intralesional, intraperitoneal, intramuscular or intravenous injection; infusion; intrathecal administration; subcutaneous administration; liposome-mediated delivery; or topical, nasal, oral, ocular or otic delivery. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         13 . The method of  claim 12 , wherein the mammal is a human. 
     
     
         14 . The method of  claim 1 , wherein the form of soluble RAGE is administered daily, weekly or monthly. 
     
     
         15 . The method of  claim 1 , wherein the therapeutically effective amount comprises a dose from about 0.000001 mg/kg body weight to about 100 mg/kg body weight. 
     
     
         16 . The method of  claim 1 , wherein the therapeutically effective amount comprises a dose from about 100 ng/kg body weight to about 200 mg/kg body weight. 
     
     
         17 . A method for evaluating the ability of an agent to inhibit tumor invasion in a local cellular environment which comprises:
 (a) admixing with cell culture media an effective amount of the agent;   (b) contacting a tumor cell in cell culture with the media from step (a);   (c) determining the amount of spreading of the tumor cell culture, and   (d) comparing the amount of spreading of the tumor cell culture determined in step (c) with the amount determined in the absence of the agent, thus evaluating the ability of the agent to inhibit tumor invasion in a local cellular environment.   
     
     
         18 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the agent further comprises a peptide, a peptidomimetic, a nucleic acid, a synthetic organic molecule, an inorganic molecule, a carbohydrate, a lipid, an antibody or fragment thereof, or a small molecule. 
     
     
         22 . The method of  claim 21 , wherein the antibody is a monoclonal antibody. 
     
     
         23 . The method of  claim 21 , wherein the antibody is a polyclonal antibody. 
     
     
         24 . The method of  claim 21 , wherein the fragment of the antibody comprises a Fab fragment. 
     
     
         25 . The method of  claim 21 , wherein the fragment of the antibody comprises a complementarity determining region or a variable region. 
     
     
         26 . The method of  claim 21 , wherein the peptide is a synthetic peptide or a peptide analog. 
     
     
         27 . The method of  claim 21 , wherein the peptide comprises at least a portion of the sequence -Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val- (SEQ ID NO:3). 
     
     
         28 . The method of  claim 21 , wherein the peptide comprises at least a portion of the sequence -Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met- (SEQ ID NO:4). 
     
     
         29 . The method of  claim 21 , wherein the peptide has the amino acid sequence A-Q-N-I-T-A-R-I-G-E-P-L-V-L-K-C-K-G-A-P-K-K-P-P-Q-R-L-E-W-K (SEQ ID NO:5). 
     
     
         30 . The method of  claim 21 , wherein the peptide has the amino acid sequence A-Q-N-I-T-A-R-I-G-E (SEQ ID NO:6). 
     
     
         31 . The method of  claim 21 , wherein the agent is a form of soluble human RAGE. 
     
     
         32 . The method of  claim 21 , wherein the agent is an extracellular portion of human RAGE. 
     
     
         33 . The method of  claim 21 , wherein the agent inhibits an interaction between the tumor cell and an extracellular matrix molecule. 
     
     
         34 . The method of  claim 21 , wherein the extracellular matrix molecule is a laminin, a fibronectin, amphoterin, a cadherin, an integrin or a hyaluronic acid. 
     
     
         35 . The method of  claim 34 , wherein the integrin is an αVβV integrin, an αVβIII integrin, or an αIβII integrin. 
     
     
         36 . The method of  claim 21 , wherein the agent inhibits binding of RAGE to amphoterin. 
     
     
         37 . The method of  claim 21 , wherein the agent binds to RAGE. 
     
     
         38 . The method of  claim 21 , wherein the agent binds to amphoterin. 
     
     
         39 . A pharmaceutical composition which comprises a therapeutically effective amount of an agent which comprises a V domain of soluble Receptor for Advanced Glycation Endproducts (RAGE) and a pharmaceutically acceptable carrier. 
     
     
         40 . (canceled) 
     
     
         41 . A method for inhibiting tumor invasion or metastasis in a subject which comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of  claim 39 .