Method for identifying anti-cancer agents using an in vitro cell culture system that maintains cancer cell stemness

Abstract

An in vitro co-culture system comprising cancer-associated fibroblasts (CAFs) and cancer cells for producing and maintaining cancer stem cells and uses thereof for identifying agents capable of reducing cancer cell stemness. Also disclosed herein are a paracrine network through which CAFs facilitate production and/or maintenance of cancer stem cells and the use of components of such a paracrine network for prognosis purposes and for identifying cancer patients who are likely to respond to certain treatment.

1 - 59 . (canceled) 
     
     
         60 . A method for treating lung cancer, comprising administering to a subject in need thereof an effective amount of an anti-lung cancer drug, wherein the subject is a lung cancer patient having an elevated level of IGF-II in cancer-associated fibroblasts (CAFs) and an elevated level of IGF1R or Nanog in cancer stem cells. 
     
     
         61 . The method of  claim 60 , wherein the anti-lung cancer drug is a drug that interferes with the IGF-II/IGF1R signaling pathway. 
     
     
         62 . The method of  claim 61 , wherein the drug is an antibody that specifically binds IGF-II or IGF1R. 
     
     
         63 . A method for identifying and treating a lung cancer patient, the method comprising:
 (i) providing a tumor tissue of a lung cancer patient;   (ii) measuring the level of IGF-II expressed in cancer-associated fibroblasts (CAFs) in the tumor tissue;   (iii) measuring the level of IGF1R, Nanog, or both expressed in cancer cells in the tumor tissue;   (iv) comparing the IGF-II level and the IGF1R or Nanog level measured in steps (ii) and (iii) with predetermined values for IGF-II and IGF1R or Nanog, respectively; and   (v) treating the lung cancer patient with an anti-lung cancer therapy wherein the level of IGF-II and the level of IGF1R and/or Nanog of the cancer patient deviate from the predetermined values.   
     
     
         64 . The method of  claim 63 , wherein the level of IGF-II and the level of IGF1R, Nanog, or both are measured by immunohistochemistry. 
     
     
         65 . The method of  claim 63 , wherein the cancer patient has non-small cell lung cancer. 
     
     
         66 . The method of  claim 63 , The wherein the anti-lung cancer therapy comprises chemotherapy, irradiation therapy, and/or an anti-cancer drug. 
     
     
         67 . The method of  claim 63 , wherein the anti-cancer therapy comprises a drug that interferes with the IGF-II/IGF1R signaling pathway. 
     
     
         68 . The method of  claim 67 , wherein the drug is an antibody that specifically binds IGFII or IGF1R.