Characterization of a Side Population of Cancer Cells from Human Gastrointestinal System

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  • Naotsugu Haraguchi
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  • Tohru Utsunomiya
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  • Hiroshi Inoue
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  • Fumiaki Tanaka
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  • Koshi Mimori
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan
  • Graham F. Barnard
    Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Masaki Mori
    Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan

抄録

<jats:title>Abstract</jats:title><jats:p>A subset of stem cells, termed “side population” (SP) cells, has been identified and characterized in several mammalian tissues and cell lines. However, SP cells have never been identified or isolated from gastrointestinal cancers. We used flow cytometry and the DNA-binding dye Hoechst 33342 to isolate SP cells from various human gastrointestinal system cancer cell lines. Fifteen of sixteen cancer cell lines from the gastrointestinal system contained 0.3%–2.2% SP cells. Next, we used an oligonucleotide microarray to analyze differentially expressed genes between SP and non-SP cells of hepatoma HuH7. The expression of GATA6, which is associated with embryonic development and hepatocytic differentiation, was significantly upregulated in HuH7 SP cells. The expression of ABCG2, ABCB1, and CEACAM6, which are associated with chemoresistance, was also significantly increased in SP cells. In addition, some epithelial markers and mesenchymal markers were overexpressed in SP cells. Reverse transcription-polymerase chain reaction and immunocytochemical staining validated these results and suggested a multilineage potential for HuH7 SP cells. In hepatoma HuH7 and colorectal SW480 cell lines, SP cells showed evidence for self-renewal, generating both SP and non-SP cells. Finally, chemoresistance to anticancer agents, including doxorubicin, 5-fluorouracil, and gemcitabine, were compared between HuH7 SP and non-SP cells using an ATP bioluminescence assay. The HuH7 SP cells expressed a higher resistance to doxorubicin, 5-fluorouracil, and gemcitabine compared with non-SP cells. These findings demonstrate that cancers of the gastrointestinal system do contain SP cells that show some characteristics of so-called stem cells.</jats:p>

収録刊行物

  • Stem Cells

    Stem Cells 24 (3), 506-513, 2005-10-20

    Oxford University Press (OUP)

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