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Identification and expansion of human colon-cancer-initiating cells

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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Figure 1: A rare CD133 + population of tumorigenic cells is present in colon cancer.
Figure 2: The tumorigenic potential of CD133 + colon cancer cells is lost upon differentiation.
Figure 3: Long-term tumorigenic potential of colon cancer CD133 + cells.

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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.

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Correspondence to Ruggero De Maria.

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Ricci-Vitiani, L., Lombardi, D., Pilozzi, E. et al. Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111–115 (2007). https://doi.org/10.1038/nature05384

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