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Identification and expansion of human colon-cancer-initiating cells

Nature volume 445, pages 111115 (04 January 2007) | Download Citation

Abstract

Colon carcinoma is the second most common cause of death from cancer1. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance2,3,4, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form tumours. Such tumours were serially transplanted for several generations, in each of which we observed progressively faster tumour growth without significant phenotypic alterations. Unlike CD133- cells, CD133+ colon cancer cells grew exponentially for more than one year in vitro as undifferentiated tumour spheres in serum-free medium, maintaining the ability to engraft and reproduce the same morphological and antigenic pattern of the original tumour. We conclude that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.

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Acknowledgements

We thank A. Zeuner for discussions. This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro and the Italian Health Ministry to R.D.M. Author Contributions Experimental work and data analysis were done by L.R.-V., D.G.L., E.P., M.B. and M.T.; project planning and supervision was done by R.D.M.

Author information

Affiliations

  1. Department of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy

    • Lucia Ricci-Vitiani
    • , Mauro Biffoni
    • , Cesare Peschle
    •  & Ruggero De Maria
  2. Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande 95029, Catania, Italy

    • Dario G. Lombardi
    •  & Ruggero De Maria
  3. Department of Laboratory Medicine and Pathology, Sant'Andrea Hospital, University ‘La Sapienza’, Via di Grottarossa 1037, Rome 00189, Italy

    • Emanuela Pilozzi
  4. Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, Palermo 90127, Italy

    • Matilde Todaro

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to Ruggero De Maria.

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    Supplementary Notes

    This file contains Supplementary Figures 1-4, Supplementary Methods, Supplementary Table 1 and Supplementary Notes.

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https://doi.org/10.1038/nature05384

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