Abstract
Background
Previous reports have demonstrated that CD133+ cells or CD44+ cells might be cancer initiating cells (CIC) of colon cancer. However, the association between the two cell types is unclear. In this study, we evaluated the tumorigenicity of each population of human colon cancer divided by CD133 and CD44 using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice.
Methods
Using the colon cancer cell lines HT29 and Caco2 we evaluated the change of expression status of CD133 or CD44 by a treatment with sodium butyrate (NaBT) that can induce cellular differentiation. Next, we prepared ten clinical samples of colon cancer and analyzed the expression and tumorigenicity of CD133 and CD44.
Results
With NaBT treatment, CD44 expression was greatly downregulated in both HT29 and Caco2 (HT29: nontreatment versus treatment; 77.8% versus 0.6%, Caco2: 14.0% versus 0.4%, respectively), more than CD133 expression (HT29: nontreatment versus treatment; 90.1% versus 67.7%, Caco2: 98.9% versus 76.3%, respectively). In clinical samples, the percentages of CD133+ cells and CD44+ cells varied from 0.3% to 82.0% (mean 35.5%), and from 11.5% to 58.4% (mean 30.0%), respectively. Subcutaneous injection of CD133+ or CD44+ cells made a tumor in all mice (3/3 and 4/4, respectively). The combined analysis of CD133 and CD44 revealed that only the CD133+CD44+ population had the ability to produce a tumor (3/3).
Conclusion
The findings demonstrate that, at present, the CD133+CD44+ population may be the best to identify tumor initiating cells of human colon cancer.
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Acknowledgements
This study was supported by CREST of Japan, Science and Technology Agency; a Grant-in-Aid for Scientific Research (S) (17109013) from the Japan Society for the Promotion of Science; a Grant-in-Aid for Scientific Research on Priority Areas (17015032) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Grant for The Third Term Comprehensive Ten-year Strategy for Cancer Control, and a Grant for Cancer Research from the Ministry of Health, Labor and Welfare of Japan.
The authors would like to thank Miss T. Shimooka, Miss Y. Nakagawa, and Miss M. Kasagi for their excellent technical assistance.
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Naotsugu Haraguchi: Awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research (Japan) for the 3rd Term Comprehensive 10- Year Strategy for Cancer Control.
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Haraguchi, N., Ohkuma, M., Sakashita, H. et al. CD133+CD44+ Population Efficiently Enriches Colon Cancer Initiating Cells. Ann Surg Oncol 15, 2927–2933 (2008). https://doi.org/10.1245/s10434-008-0074-0
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DOI: https://doi.org/10.1245/s10434-008-0074-0