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10.1245/s10434-007-9605-3
Annals of Surgical Oncology 15:638-648 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Biological and Genetic Characteristics of Tumor-Initiating Cells in Colon Cancer

Keisuke Ieta, MD, PhD1,2, Fumiaki Tanaka, MD, PhD1, Naotsugu Haraguchi, MD, PhD1, Yoshiaki Kita, MD1, Hiroyuki Sakashita, MD1, Koshi Mimori, MD, PhD1, Toshifumi Matsumoto, MD, PhD1, Hiroshi Inoue, MD, PhD1, Hiroyuki Kuwano, MD, PhD2 and Masaki Mori, MD, PhD1

1 Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan
2 Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, Japan

Correspondence: Address correspondence and reprint requests to: Masaki Mori, MD, PhD; E-mail: mmori{at}tsurumi.beppu.kyushu-u.ac.jp

Background: Human prominin-1 (PROM1, CD133) was used as a marker to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating cells) in various tissues. The purpose of this study was to investigate the biological and genetic characteristics of tumor-initiating cells in colon cancer with both in vitro and in vivo analyses.

Methods: The CD133 expression of 12 colon cancer cell lines was evaluated. CD133+ cells were isolated by flow cytometry and examined for in vivo tumor formation, in vitro proliferation, colony formation, and invasion ability. Additionally, we used microarray analysis to compare gene expression profiles between CD133+ and CD133– isolated cells.

Results: CD133+ cells were found in 5 of 12 colon cancer cell lines. Isolated CD133+ cells from the HT29 colon cancer cell line exhibited a higher tumorigenic potential than CD133– cells in the in vivo tumor formation assay. Furthermore, it was shown that CD133+ cells are more proliferative and have higher colony-forming and invasive abilities than CD133– cells in vitro. Microarray analysis found differential gene expression correlating with CD133 expression.

Conclusions: It was confirmed that CD133+ cells in colon cancer are useful markers for the detection of tumor-initiating cells. Intimate biological and genetic features of CD133+ cells in colon cancer cell lines were also revealed. The biological characteristics of CD133+ cells and differentially expressed genes in these cells will help elucidate more details of tumor-initiating cells in colon cancer.

Key Words: Colon cancer • Stem cells • Tumor-initiating cells • CD133






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