Use of FVIIa or a tissue factor antagonist for regulating gene expression and cell migration or chemotaxis

Abstract

The present invention relates to use of FVII and/or FVIIa and/or another TF agonist and/or FVIIai and/or another TF antagonist in therapeutic treatment of pathological conditions that can be related to cell migration or treated by specific regulation of cell migration or chemotaxis. The invention also relates to the use of of FVII and/or FVIIa and/or another TF agonist and/or FVIIai and/or another TF antagonist in therapeutic treatment of pathological conditions that can be related to regulation of expression of at least one gene in a cell, e.g., Cyr61 gene.

1 . A method for inducing or enhancing cell migration, comprising the step of contacting said cell with a tissue factor agonist  
     
     
         2 . The method of  claim 1 , wherein the tissue factor agonist is FVII or FVIIa.  
     
     
         3 . A method of reducing or inhibiting cell migration, comprising the step of contacting the cell with a tissue factor antagonist.  
     
     
         4 . The method of  claim 3 , wherein the tissue factor antagonist is modified FVII.  
     
     
         5 . The method of  claim 1  or  claim 3 , wherein said cell is a human cell expressing tissue factor, including fibroblasts, smooth muscle cells, tumour cells, haematopoietic cells, monocytes, macrophages and epithelial cells.  
     
     
         6 . The method of  claim 5 , wherein said cell further expresses PDGF and PDGF receptors, especially PDGF beta-receptors.  
     
     
         7 . The method according to  claim 4 , wherein the modified factor VII is selected from factor VII modified with Dansyl-Phe-Phe-Arg chloromethyl ketone, Phe-Phe-Arg chloromethylketone, Dansyl-D-Phe-Phe-Arg chloromethyl ketone and D-Phe-Phe-Arg chloromethylketone.  
     
     
         8 . A method for inducing or enhancing wound healing in a patient, comprising administering to said patient an effective amount of a pharmaceutical composition comprising Factor VIIa or factor VII or another tissue factor agonist.  
     
     
         9 . A method for inhibiting or reducing cell migration, invasion, migration-induced cell proliferation or angiogenesis in a patient having a disease or condition associated with undesired cell migration, invasion, migration-induced cell proliferation or angiogenesis, comprising administering to said patient an effective amount of a pharmaceutical composition comprising a tissue factor antagonist.  
     
     
         10 . A method according to  claim 9 , wherein the disease or condition is primary tumour growth, tumour invasion or metastasis.  
     
     
         11 . A method according to  claim 9 , wherein the tissue factor antagonist is modified factor VII.  
     
     
         12 . Use of a tissue factor agonist for the manufacture of a medicament for inducing or enhancing cell migration.  
     
     
         13 . Use according to  claim 12 , wherein the tissue factor agonist is FVII or FVIIa or a combination thereof.  
     
     
         14 . Use of a tissue factor antagonist for the manufacture of a medicament for reducing or inhibiting cell migration.  
     
     
         15 . The use of  claim 14 , wherein the tissue factor antagonist is modified factor VII.  
     
     
         16 . Use according to  claim 15 , wherein the modified factor VII is selected from factor VII modified with Dansyl-Phe-Phe-Arg chloromethyl ketone, Phe-Phe-Arg chloromethylketone, Dansyl-D-Phe-Phe-Arg chloromethyl ketone and D-Phe-Phe-Arg chloromethylketone.  
     
     
         17 . A method of regulating the expression of at least one gene in a cell, comprising the step of contacting said cell with a tissue factor agonist or a tissue factor antagonist, under conditions that result in a measurable change in said expression.  
     
     
         18 . The method of  claim 17 , wherein the tissue factor agonist is selected from the group consisting of FVII, FVIIa, and combinations thereof.  
     
     
         19 . The method of  claim 17 , wherein the tissue factor antagonist is modified FVII.  
     
     
         20 . The method of  claim 19 , wherein the modified factor VII is selected from the group consisting of factor VII modified with Dansyl-Phe-Phe-Arg chloromethyl ketone, Phe-Phe-Arg chloromethylketone, Dansyl-D-Phe-Phe-Arg chloromethyl ketone and D-Phe-Phe-Arg chloromethylketone.  
     
     
         21 . The method of  claim 17 , wherein the gene is a gene belonging to the CCN gene family.  
     
     
         22 . The method of  claim 17 , wherein said gene is selected from the group consisting of Cyr61, CTFG, dopamine D2 receptor, EST Incyte PD 395116 and P2U nucleotide receptor.  
     
     
         23 . The method of  claim 21 , wherein the gene is Cyr61 gene.