Differential gene expression in physiological and pathological angiogenesis

Abstract

Methods of inhibiting pathological angiogenesis in a subject are disclosed. In particular examples, the method includes administering a therapeutically effective amount of a composition to a subject wherein the composition includes a specific binding agent that preferentially binds to one or more pathological angiogenesis marker proteins including Vscp, CD276, ETSvg4 (Pea3), CD137(4-1BB), MiRP2, Ubiquitin D (Fat10), Doppel (prion-PLP), Apelin, Plgf, Ptprn (IA-2), CD109, Ankylosis, and collagen VIIIα1. In additional examples, methods to deliver a therapeutic agent to a brain or liver endothelial cell are also disclosed.

1 . A method of determining pathological angiogenesis, comprising:
 a) contacting a sample obtained from a subject with a first probe, antibody, or primer set capable of detecting at least a first expression product selected from the group consisting of Vscp, ETSvg4 (Pea3), CD137(4-1BB), MiRP2, Ubiquitin D (Fat10), Doppel (prion-PLP), Apelin, Plgf, CD109, Ankylosis, and collagen VIII and a second probe, antibody, or primer set capable of detecting at least a second expression product selected from the group consisting of Vscp, ETSvg4 (Pea3), CD137(4-1BB), MiRP2, Ubiquitin D (Fat10), Doppel (prion-PLP), Apelin, Plgf, CD109, Ankylosis, and collagen VIII, in a sample obtained from the subject;   b) detecting the at least first expression product and the at least second expression product in the sample obtained from the subject by performing an assay that detects both the at least first and second expression products; and   c) determining the presence of pathological angiogenesis in the subject by comparing expression level of the first expression product and the second expression product in the sample obtained from the subject with the expression level of the first expression product and second expression product in a control sample, wherein detection of an increase in expression of the at least first and second expression products as compared to expression of the at least first and second expression products in a control sample indicates pathological angiogenesis.   
     
     
         2 . The method of  claim 1 , wherein detection of an increase in expression of the at least first and second expression products indicates the presence of a tumor. 
     
     
         3 . The method of  claim 2 , wherein the expression products are RNA or protein. 
     
     
         4 . The method of  claim 2 , wherein the tumor is a cancer of the colon, liver, lung, breast, or ovary. 
     
     
         5 . The method of  claim 1 , wherein the detecting the at least first and second expression products is performed using serial analysis gene expression (SAGE), polymerase chain reaction, Western blot, immunoassay, microscopy, flow cytometry, spectrometry, or a combination thereof. 
     
     
         6 . The method of  claim 1 , wherein the sample is serum sample. 
     
     
         7 . The method of  claim 1 , wherein the method is used to detect the efficacy of an anti-angiogenic agent for treating pathological angiogenesis. 
     
     
         8 - 20 . (canceled) 
     
     
         21 . The method of  claim 2 , wherein the tumor is a sarcoma. 
     
     
         22 . The method of  claim 2 , wherein the tumor is a CNS tumor. 
     
     
         23 . The method of  claim 22 , wherein the CNS tumor is a glioma. 
     
     
         24 . The method of  claim 1 , further comprising d) treating the subject for pathological angiogenesis and/or cancer. 
     
     
         25 . The method of  claim 1 , wherein the subject is a veterinary subject. 
     
     
         26 . The method of  claim 24 , wherein the veterinary subject is a dog.