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.

TODARO, M., PEREZ ALEA, M., DI STEFANO, A.B., CAMMARERI, P., VERMEULEN, L., IOVINO, F., et al. (2007). Colon Cancer Stem Cells Dictate Tumor Growth and Resist Cell Death by Production of Interleukin-4. CELL STEM CELL, 1, 389-402 [10.1016/J.STEM.2007.08.001].

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

TODARO, Matilde;PEREZ ALEA, Milidys;DI STEFANO, Anna Barbara;CAMMARERI, Patrizia;IOVINO, Flora;TRIPODO, Claudio;RUSSO, Antonio;GULOTTA, Gaspare;STASSI, Giorgio
2007

Abstract

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.
TODARO, M., PEREZ ALEA, M., DI STEFANO, A.B., CAMMARERI, P., VERMEULEN, L., IOVINO, F., et al. (2007). Colon Cancer Stem Cells Dictate Tumor Growth and Resist Cell Death by Production of Interleukin-4. CELL STEM CELL, 1, 389-402 [10.1016/J.STEM.2007.08.001].
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S193459090700118X-main.pdf

accesso aperto

Dimensione 756.23 kB
Formato Adobe PDF
756.23 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/13816
Citazioni
  • ???jsp.display-item.citation.pmc??? 406
  • Scopus 847
  • ???jsp.display-item.citation.isi??? 809
social impact