Gastrointestinal Oncology

Annals of Surgical Oncology

, Volume 15, Issue 10, pp 2927-2933

CD133+CD44+ Population Efficiently Enriches Colon Cancer Initiating Cells

  • Naotsugu HaraguchiAffiliated withDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University
  • , Masahisa OhkumaAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Hiroyuki SakashitaAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Shinji MatsuzakiAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Fumiaki TanakaAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Koshi MimoriAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Yukio KamoharaAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Hiroshi InoueAffiliated withDepartment of Surgery, Medical Institute of Bioregulation, Kyushu University
  • , Masaki MoriAffiliated withDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University Email author 

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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.

Keywords

CD133 CD44 Colon cancer Colon cancer initiating cells Sodium butyrate