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Letter
Nature 445, 111-115 (4 January 2007) | doi:10.1038/nature05384; Received 20 September 2006; Accepted 30 October 2006; Published online 19 November 2006
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Identification and expansion of human colon-cancer-initiating cells
Lucia Ricci-Vitiani1, Dario G. Lombardi2, Emanuela Pilozzi3, Mauro Biffoni1, Matilde Todaro4, Cesare Peschle1 & Ruggero De Maria1,2
- Department of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy
- Mediterranean Institute of Oncology, Via Penninazzo 7, Viagrande 95029, Catania, Italy
- Department of Laboratory Medicine and Pathology, Sant'Andrea Hospital, University 'La Sapienza', Via di Grottarossa 1037, Rome 00189, Italy
- Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, Palermo 90127, Italy
Correspondence to: Ruggero De Maria1,2 Correspondence and requests for materials should be addressed to R.D.M. (Email: rdemaria@tin.it).
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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