Human colon cancer stem cells locate in hypoxic niche

Abstract

22209 Background: It has been proposed that a small number of undifferentiated tumorigenic CD133+ cells from human colon carcinoma be defined as colon cancer stem cells (CSCs) based on their self-renewal and propagation properties. In order to further investigate the CSCs niche, we applied an approach to resolve the spatial organization of human colon cancer stem cells according to hypoxia and the impact of hypoxia on irradiation. Methods: Eight fresh samples of primary human colon cancers were implanted in immunocompromised mice. The percentage of hypoxic CD133+ cell population was detected and quantified by use of hypoxic maker pimonidazole (PIM) via flow-cytometry. Measurements were also made of CD133+ cell population and its change of hypoxic situation following irradiation with a single dose of 2 Gy, 5 Gy, 10 Gy, and 20 Gy, respectively. Results: CD133+ cells were found to be the most positive for binding of PIM. The percentage of hypoxic population of CD133+ cells were ranged from 51.6% to 87.0% with an average of 70.2%, whereas the other colon cancer cells labeled CD133- demonstrated an average of 20.2% ranged from 5.3% to 49.1%. Hypoxic population of CD133+ cells was 4.5 times (from 2 to 12 times) than that of CD133- cells. Compared with control, irradiation at 2 Gy to 20 Gy with a single fraction reduced the CD133+ cell population in period of 1 to 6 hours after treatment. Interestingly, it resulted in an increase of the percentage of hypoxic CSCs to different extent rather than other hypoxic colon cancer cells. Conclusions: Most population of human colon CSCs locate in hypoxic niche, and the hypoxic human colon CSCs resist radiotherapy to some extent. It is implicated that regionally defined hypoxia plays a fundamental role in both regulating human colon CSCs function and diminishing therapeutic response. No significant financial relationships to disclose.