Colon Cancer Stem Cells Dictate Tumor Growth and Resist Cell Death by Production of Interleukin-4

Claudio Tripodo, Flora Iovino, Matilde Todaro, Giorgio Stassi, Antonio Russo, Gaspare Gulotta, Anna Barbara Di Stefano, Patrizia Cammareri, Louis Vermeulen, Mileidys Perez Alea, Antonio Russo, Anna B. Di Stefano, Giorgio Stassi, Jan Paul Medema, Matilde Todaro, Flora Iovino, Mileidys Perez Alea

Risultato della ricerca: Articlepeer review

805 Citazioni (Scopus)


A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133+ cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133+ cells. Further analysis revealed that the CD133+ cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, treatment with IL-4Rα antagonist or anti-IL-4 neutralizing antibody strongly enhances the antitumor efficacy of standard chemotherapeutic drugs through selective sensitization of CD133+ cells. Our data suggest that colon tumor growth is dictated by stem-like cells that are treatment resistant due to the autocrine production of IL-4.
Lingua originaleEnglish
pagine (da-a)389-402
Numero di pagine14
RivistaCell Stem Cell
Stato di pubblicazionePublished - 2007

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1311???
  • ???subjectarea.asjc.1300.1307???


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