Enhanced resolution of tumor metastasis using a skin flap model

Abstract

A enhanced method for observing tumor progression, angiogenesis and/or metastasis in animal models in real time is described. The invention employs a skin flap over the area to be observed that can be opened and closed reversibly. The invention also permits simultaneous observation of more than one tumor by use of multiple colors.

1 . A method to evaluate the effect of a compound or protocol on cancer progression, angiogenesis and/or metastasis, which method comprises
 performing the method of  claim 1  in the presence and absence of the compound or protocol to be tested, and   comparing the results obtained,   whereby the effect of said compound or protocol on cancer progression, angiogenesis, and/or metastasis is evaluated.   
   
   
       2 . The method  claim 1 , wherein the immunocompromised experimental animal is a mouse or rat. 
   
   
       3 . The method of  claim 1 , wherein said fluorescent tumor cells have been modified to contain a nucleic acid molecule for expression of a fluorescent protein. 
   
   
       4 . The method of  claim 3 , wherein the fluorescent protein emits green fluorescence. 
   
   
       5 . The method of  claim 3 , wherein the fluorescent protein emits red fluorescence. 
   
   
       6 . The method of  claim 1 , wherein the experimental animal is provided tumor cells by subcutaneous injection. 
   
   
       7 . The method of  claim 1 , wherein the experimental animal is provided tumor tissue by surgical orthological implantation (SOI). 
   
   
       8 . The method of  claim 1 , wherein the tumor tissue is endogenous and is made fluorescent by infecting with a viral vector for expression of fluorescent proteins. 
   
   
       9 . The method of  claim 1 , wherein the skin flap is an arc-shaped flap. 
   
   
       10 . The method of  claim 1 , wherein the tumor cells are tissues or of brain, lung, liver, colon, breast, prostate, ovary or pancreas. 
   
   
       11 . The method of  claim 1 , wherein the observing is macroscopic. 
   
   
       12 . The method of  claim 1 , wherein the observing is microscopic. 
   
   
       13 . The method of  claim 1 , wherein said tumor cells or tissue comprise nucleic acid molecules for production of fluorescent proteins of at least two different colors. 
   
   
       14 . A method to observe simultaneously, the progression, angiogenesis and/or metastasis of at least first and second tumor cells or tissues, which method comprises
 the step of providing at least a first tumor cell or tissue which is modified to express a first fluorescent protein that emits a first color and a second cell or tissue which is modified to express a second fluorescent protein which emits a second color; and   observing said cells or tissues in an immunocompromised or syngeneic experimental animal.   
   
   
       15 . The method of  claim 14 , wherein said first tumor cells are tissues are of different origin from said second cells or tissues. 
   
   
       16 . The method of  claim 14 , wherein said cells are tissues are of prostate, breast, or fibrosarcoma. 
   
   
       17 . The method of  claim 14 , wherein said first and second tumor cells have been modified to contain a nucleic acid molecule for expression of a fluorescent protein. 
   
   
       18 . The method of  claim 17 , wherein the fluorescent protein emits green fluorescence. 
   
   
       19 . The method of  claim 17 , wherein the fluorescent protein emits red fluorescence.