Identification and enrichment of cell subpopulations

Abstract

Markers useful for the identification, characterization and, optionally, the enrichment or isolation of tumorigenic cells or cell subpopulations are disclosed.

1 - 20 . (canceled) 
     
     
         21 . An animal model for the analysis of pharmaceutical compounds comprising a subject animal implanted with a cell population derived from a primary tumor sample or a passaged tumor sample and enriched as to tumorigenic cells, wherein at least 40% of the cells within the cell population comprise a CD46 hi marker phenotype. 
     
     
         22 . The animal model of  claim 21 , wherein the cell population is derived from a solid tumor. 
     
     
         23 . The animal model of  claim 22 , wherein the solid tumor is obtained from a subject suffering from a neoplastic disorder selected from the group consisting of adrenal cancer, bladder cancer, cervical cancer, endometrial cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, head & neck cancer, and skin cancer. 
     
     
         24 . The animal model of  claim 21 , wherein the subject animal comprises an animal species selected from the group consisting of mouse, rat, rabbit, dog, pig, sheep and primate. 
     
     
         25 . The animal model of  claim 24 , wherein the animal species comprises an immunodeficient mouse. 
     
     
         26 . The animal model of  claim 25  wherein the immunodeficient mouse is selected from the group consisting of nude mice, SCID mice, NOD/SCID mice and Beige/SCID mice. 
     
     
         27 . The animal model of  claim 26  wherein the immunodeficient mouse comprises a NOD/SCID mouse. 
     
     
         28 . The animal model of  claim 21 , wherein the cell population comprises a human cell population. 
     
     
         29 . The animal model of  claim 21 , wherein the tumorigenic cells have a marker phenotype comprising CD46 hi  CD324 + . 
     
     
         30 . A non-human subject comprising at least one tumor wherein said tumor is generated from an isolated CD46 hi  CD324 +  tumorigenic cell or an enriched tumorigenic cell population comprising a CD46 hi  CD324 +  marker phenotype following introduction into said non-human subject. 
     
     
         31 . The non-human subject of  claim 30 , wherein said tumorigenic cell or enriched tumorigenic cell population is derived from a solid tumor. 
     
     
         32 . The non-human subject of  claim 31 , wherein said solid tumor is obtained from a subject suffering from a neoplastic disorder selected from the group consisting of adrenal cancer, bladder cancer, cervical cancer, endometrial cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, head & neck cancer, and skin cancer. 
     
     
         33 . The non-human subject of  claim 30 , wherein said subject comprises an animal species selected from the group consisting of mouse, rat, rabbit, dog, pig, sheep and primate. 
     
     
         34 . The non-human subject of  claim 33 , wherein the animal species comprises an immunodeficient mouse. 
     
     
         35 . The non-human subject of  claim 34  wherein said immunodeficient mouse is selected from the group consisting of nude mice, SCID mice, NOD/SCID mice and Beige/SCID mice. 
     
     
         36 . A method of conducting genotypic analysis comprising the steps of:
 (a) providing a tumor sample comprising dissociated tumor cells;   (b) contacting the tumor sample with a binding agent that binds to CD46 to provide labeled tumor cells;   (c) sorting the labeled tumor cells by flow cytometry to provide an enriched tumorigenic cell population comprising tumorigenic cells, wherein at least 40% of the cells within the enriched tumorigenic cell population comprise a CD46 hi  marker phenotype;   (d) obtaining genetic material from the enriched tumorigenic cell population; and   (e) analyzing the genetic material.   
     
     
         37 . The method of  claim 36 , wherein step (b) comprises further contacting the tumor sample with a binding agent that binds to CD324, and wherein the enriched tumorigenic cell population of step (c) comprises CD324 +  tumorigenic cells. 
     
     
         38 . The method of  claim 36 , wherein the tumor sample is obtained from a subject suffering from a neoplastic disorder selected from the group consisting of adrenal cancer, bladder cancer, cervical cancer, endometrial cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, colorectal cancer, pancreatic cancer, prostate cancer, breast cancer, head and neck cancer, and melanoma. 
     
     
         39 . The method of  claim 36 , wherein the binding agent comprises a genotypic binding agent. 
     
     
         40 . The method of  claim 36 , wherein the binding agent comprises a phenotypic binding agent. 
     
     
         41 . The method of  claim 36 , wherein the phenotypic binding agent comprises an antibody. 
     
     
         42 . The method of  claim 36 , wherein the tumor sample is derived from a solid tumor. 
     
     
         43 . The method of  claim 36 , wherein the tumor sample is obtained from a tumor that has been passaged through a non-human mammal.