Prospective Identification and Characterization of Breast Cancer Stem Cells

Abstract

The invention provides methods for treating cancer via administering to a patient having a solid tumor a therapeutically effective amount of an antibody against Delta-like ligand 4(D114) or other Notch pathway components. The solid tumor may comprise solid tumor stem cells.

1 . A method for reducing the size of a solid tumor, the method comprising: providing an agent directed against an extracellular domain of a Notch4 polypeptide, and contacting cells of the solid tumor, wherein the solid tumor comprises solid tumor stem cells, with a therapeutically effective amount of the agent. 
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount is an amount sufficient to cause cell death of or inhibit the proliferation of the cells in the solid tumor. 
     
     
         3 . The method of  claim 1 , wherein the agent is an antibody directed against the extracellular domain epitope of SEQ ID NO: 1. 
     
     
         4 . A method for reducing the size of a solid tumor, the method comprising: providing an agent directed against a Notch4 ligand and contacting cells of the solid tumor, wherein the solid tumor comprises solid tumor stem cells, with a therapeutically effective amount of the agent. 
     
     
         5 . The method of  claim 4 , wherein the Notch4 ligand is Delta 1. 
     
     
         6 . The method of  claim 4 , wherein the Notch4 ligand is Delta 2. 
     
     
         7 . The method of  claim 4 , wherein the Notch4 ligand is Delta-like ligand 4 (D114). 
     
     
         8 . The method of  claim 4 , wherein the Notch4 ligand is Jagged 1. 
     
     
         9 . The method of  claim 4 , wherein the Notch4 ligand is Jagged 2. 
     
     
         10 . The method of  claim 4 , wherein the therapeutically effective amount is an amount sufficient to cause cell death of or inhibit the proliferation of the cells in the solid tumor. 
     
     
         11 . The method of  claim 1 , wherein the solid tumor stem cells express at least one marker selected from CD44, epithelial specific antigen (ESA), and B38.1. 
     
     
         12 . The method of  claim 1 , wherein the solid tumor stem cells express the cell surface marker CD44. 
     
     
         13 . The method of  claim 1 , wherein the solid tumor stem cells express the cell surface marker epithelial specific antigen (ESA). 
     
     
         14 . The method of  claim 1 , wherein the solid tumor stem cells express the cells surface maker B38.1. 
     
     
         15 . The method of  claim 1 , wherein the solid tumor stem cells express lower levels of the maker CD24 than the mean expression of CD24 by non-tumorigenic cancer cells of the solid tumor. 
     
     
         16 . The method of  claim 1 , wherein the solid tumor stem cells fail to express at least one LINEAGE maker selected from CD2, CD3, CD10, CD14, CD16, CD31, CD45, CD64, and CD140b. 
     
     
         17 . The method of  claim 1 , wherein the solid tumor is an epithelial cancer or a sarcoma. 
     
     
         18 . The method of  claim 1 , wherein the epithelial cancer is a breast cancer or an ovarian cancer. 
     
     
         19 . The method of  claim 4 , wherein the solid tumor stem cells express at least one marker selected from CD44, epithelial specific antigen (ESA), and B38.1. 
     
     
         20 . The method of  claim 4 , wherein the solid tumor stem cells express the cell surface marker CD44.