Isolation and use of solid tumor stem cells

Abstract

A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

1 - 185 . (canceled)  
     
     
         186 . A method for diagnosing the presence of solid tumor stem cells in a patient having a solid tumor, comprising: 
 (a) obtaining a sample comprising the solid tumor stem cells from the patient;    (b) contacting the sample with a reagent that binds to a positive marker for solid tumor stem cells; and    (c) detecting the presence of the solid tumor stem cells in the sample, thereby identifying the presence of the solid tumor stem cells in the patient.    
     
     
         187 . The method of  claim 186 , wherein the detecting step (c) is by flow-cytometry or immunohistochemistry.  
     
     
         188 . The method of  claim 186 , wherein the solid tumor is of epithelial origin.  
     
     
         189 . The method of  claim 186 , wherein the solid tumor is a sarcoma.  
     
     
         190 . The method of  claim 186 , wherein the solid tumor is a breast cancer tumor.  
     
     
         191 . The method of  claim 186 , wherein the positive marker comprises CD44.  
     
     
         192 . The method of  claim 186 , wherein the positive marker comprises B38.1.  
     
     
         193 . The method of  claim 186 , wherein the positive marker comprises ESA.  
     
     
         194 . The method of  claim 186 , wherein step (b) further comprises contacting the sample with a second reagent that binds to a negative marker for the solid tumor stem cells.  
     
     
         195 . The method of  claim 194 , wherein the negative marker comprises CD24.  
     
     
         196 . The method of  claim 194 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD10, CD14, CD16, CD19, CD31, CD45, CD64, and CD140b.  
     
     
         197 . The method of  claim 194 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD 10, CD31, and CD140b.  
     
     
         198 . The method of  claim 194 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD10, CD14, CD16, CD31, and CD 140b.  
     
     
         199 . A method for selecting a treatment for a patient having a solid tumor, comprising: 
 (a) obtaining a sample from the patient;    (b) identifying the presence of a solid tumor stem cell in the sample; and    (c) selecting a treatment for the patient that targets solid tumor stem cells.    
     
     
         200 . The method of  claim 199 , wherein the solid tumor is of epithelial origin.  
     
     
         201 . The method of  claim 199 , wherein the solid tumor is a sarcoma.  
     
     
         202 . The method of  claim 199 , wherein the solid tumor is a breast cancer tumor.  
     
     
         203 . The method of  claim 199 , wherein step (b) of identifying the presence of the solid tumor stem cell comprises contacting the sample with a reagent that binds to a positive marker for solid tumor stem cells.  
     
     
         204 . The method of  claim 203 , wherein the positive marker comprises CD44.  
     
     
         205 . The method of  claim 203 , wherein the positive marker comprises B38.1.  
     
     
         206 . The method of  claim 203 , wherein the positive marker comprises ESA.  
     
     
         207 . The method of  claim 203 , wherein step (b) of identifying the presence of the solid tumor stem cell further comprises contacting the sample with a second reagent that binds to a negative marker for solid tumor stem cells.  
     
     
         208 . The method of  claim 207 , wherein the negative marker comprises CD24.  
     
     
         209 . The method of  claim 207 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD10, CD 14, CD16, CD19, CD31, CD45, CD64, and CD140b.  
     
     
         210 . The method of  claim 207 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD1O, CD31, and CD140b.  
     
     
         211 . The method of  claim 207 , wherein the negative marker comprises a LINEAGE marker selected from the group consisting of CD2, CD3, CD10, CD 14, CD16, CD31, and CD 140b.