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 maintenance^2,3,4, 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.