Identification and characterization of cancer stem cells and methods of use

Abstract

A subpopulation of cancer stem cells expressing elevated levels of uPAR have been identified among a population of cancer cells. Methods are provided for treating proliferative disorders such as cancer by administering one or more uPAR inhibitors. Methods are likewise provided for predicting the likelihood of recurrence of a cancer, preventing recurrence of a cancer, and identifying the likelihood of a cancer to respond to a particular cancer therapy.

1 . A method of treating cancer in a subject, comprising administering to said subject a therapeutically effective amount of a uPAR inhibitor.  
   
   
       2 . The method of  claim 1 , further comprising administering one or more anticancer agents.  
   
   
       3 . The method of  claim 2 , wherein said one or more anticancer agents are selected from the group consisting of doxorubicin, 5-fluorouracil, carboplatin, cisplatin, etoposide, cylophosphamide, vincristine, ifosfamide, topotecan, paclitaxel, methotrexate, vinorelbine, gemcitabine, irinotecan and docetaxel, and X-ray irradiation  
   
   
       4 . A method of preventing recurrence of cancer in a subject, comprising administering to said subject a therapeutically effective amount of a uPAR inhibitor.  
   
   
       5 . The method of  claim 4 , wherein said subject is in remission from cancer.  
   
   
       6 . A method of reducing or inhibiting the proliferative or invasive potential of a tumor cell, comprising delivering to said tumor cell an effective amount of a uPAR inhibitor.  
   
   
       7 . A method of determining the likelihood of recurrence of cancer in a subject diagnosed with cancer, comprising measuring uPAR expression in a cancer cell derived from said subject, wherein a greater magnitude of uPAR expression in said cancer cell as compared to a non-cancerous cell derived from the same subject indicates a greater risk of cancer recurrence.  
   
   
       8 . A method of obtaining one or more cancer stem cells from a cancer cell population, comprising sorting said cancer cell population into uPAR-positive and uPAR-negative subpopulations based on surface uPAR expression, wherein said uPAR-positive subpopulation consists of one or more cancer stem cells.  
   
   
       9 . An isolated cancer stem cell obtained by the method of  claim 8.