Isolation and use of solid tumor stem cells

Abstract

A small percentage of cells within an established solid 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. Thus, solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. We have developed a xenograft model in which we have been able to establish tumors from primary tumors via injection of tumors in the mammary gland of severely immunodeficient mice. These xenograft assay have allowed us to do biological and molecular assays to characterize clonogenic solid tumor stem cells. We have also developed evidence that strongly implicates the Notch pathway, especially Notch 4, as playing a central pathway in carcinogenesis.

1 - 185 . (canceled) 
     
     
         186 . A method for inhibiting the proliferation of cancer cells, the method comprising eradicating cancer stem cells so that production of cancer cells is reduced. 
     
     
         187 . The method of  claim 186 , wherein the cancer cells are human cancer cells. 
     
     
         188 . The method of  claim 186 , wherein an antibody or antibody fragment is used to eradicate the cancer stem cells. 
     
     
         189 . The method of  claim 188 , wherein the antibody or antibody fragment is conjugated to a moiety. 
     
     
         190 . A method for inhibiting the proliferation of cancer cells, the method comprising inducing differentiation of cancer stem cells so that production of cancer cells is reduced. 
     
     
         191 . The method of  claim 190 , wherein the cancer cells are human cancer cells. 
     
     
         192 . The method of  claim 190 , wherein a differentiation-inducing agent is used to induce differentiation of the cancer stem cells. 
     
     
         193 . The method of  claim 190 , wherein an antibody or antibody fragment is used to induce differentiation of the cancer stem cells. 
     
     
         194 . The method of  claim 190 , wherein a small molecule is used to induce differentiation of the cancer stem cells. 
     
     
         195 . The method of  claims 186  or  190  wherein the cancer stem cells are brain cancer cells, breast cancer cells, kidney cancer cells, colorectal cancer cells, prostate cancer cells, rhabdomyosarcoma cells, retinoblastoma cells, hepatic cancer cells, epidermal cancer cells, gastrointestinal cancer cells, pancreatic cancer cells, or lung cancer cells.