Compositions and methods for treating and diagnosing cancer

Abstract

The present invention relates to compositions and methods for characterizing, treating and diagnosing cancer. In particular, the present invention provides a cancer stem cell profile, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of cancer and in particular the targeting of solid tumor stem cells.

1 . An isolated population of cancer stem cells obtained from a tumor of epithelial origin, wherein the population comprises at least 75% cancer stem cells and less than 25% non-tumorigenic tumor cells, wherein the cancer stem cells:
 are tumorigenic; and,   express elevated levels of one or more of PTGFRN, CD166, CD164, CD82, TGFBR1, MET, EFNB2, ITGA6, TDGF1, HBEGF, ABCC4, ABCD3, TDE2, ITGB1, TNFRSF21, CD81, CD9, KIAA1324, CEACAM6, FZD6, FZD7, BMPR1A, JAG1, ITGAV, NOTCH2, SOX4, HES1, HES6, ATOH1, CDH1, EPHB2, MYB, MYC, SOX9, PCGF1, PCGF4, PCGF5, ALDH1A1, and STRAP, or reduced levels of one or both of TCF 4  or VIM relative to the non-tumorigenic tumor cells.   
   
   
       2 . The isolated population of cancer stem cells of  claim 1 , wherein the cancer stem cells are CD44+. 
   
   
       3 . The isolated population of cancer stem cells of  claim 1 , wherein the cancer stem cells further express epithelial specific antigen (ESA). 
   
   
       4 . The isolated population of cancer stem cells of  claim 1 , wherein the cancer stem cells are colon cancer stem cells. 
   
   
       5 . The isolated population of cancer stem cells of  claim 1 , wherein the cancer stem cells are head and neck cancer stem cells. 
   
   
       6 - 10 . (canceled) 
   
   
       11 . A method for obtaining from a tumor a cellular composition comprising cancer stem cells and non-tumorigenic tumor cells, wherein at least 75% are tumorigenic stem cells and 25% or less are non-tumorigenic tumor cells, said method comprising:
 (a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;   (b) separating the mixture of tumor cells into a first fraction comprising at least 75% cancer stem cells and 25% or less non-tumorigenic tumor cells and a second fraction of tumor cells depleted of cancer stem cells wherein the separating is by contacting the mixture with reagents against CD44 and ESA; and   (c) demonstrating the first fraction to be tumorigenic by serial injection into a first host animal and the second fraction to be non-tumorigenic by serial injection into a second host animal.   
   
   
       12 . The method of  claim 11  wherein the separating is performed by flow cytometry, fluorescence activated cell sorting (FACS), panning, affinity chromatography or magnetic selection. 
   
   
       13 . The method of  claim 11  wherein the separating, is performed by fluorescence activated cell sorters (FACS) analysis. 
   
   
       14 . The method of  claim 11  wherein the cancer stem cells are colon cancer stem cells. 
   
   
       15 . The method of  claim 11  wherein the cancer stem cells are head and neck cancer stem cells. 
   
   
       16 . A method for enriching a population of cancer stem cells from a tumor of epithelial origin wherein the enriched population comprises 75% cancer stem cells and 25% or less non-tumorigenic tumor cells, said method comprising:
 (a) obtaining a dissociated mixture of tumor cells from a tumor of epithelial origin;   (b) contacting the mixture of tumor cells with reagents against CD44 and ESA;   (c) selecting a first fraction of cancer stem cells by their binding to the reagents and a second fraction of colon tumor cells depleted of colon cancer stem cells; and   (d) demonstrating the first fraction to be tumorigenic by serial injection of the colon tumor stem cells into a host animal and the second fraction to be non-tumorigenic by serial injection into the host animal.   
   
   
       17 . The method of  claim 16  wherein the selecting is performed by flow cytometry, fluorescence activated cell sorting (FACS), panning, affinity chromatography, or magnetic selection. 
   
   
       18 . The method of  claim 16  wherein the selecting is performed by fluorescence activated cell sorters (FACS) analysis. 
   
   
       19 . The method of  claim 16  wherein the cancer stem cells are colon cancer stem cells. 
   
   
       20 . The method of  claim 16  wherein the cancer stem cells are head and neck cancer stem cells. 
   
   
       21 .- 68 . (canceled)