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Absence of CD71 Transferrin Receptor Characterizes Human Gastric Adenosquamous Carcinoma Stem Cells

Annals of Surgical Oncology volume 19, pages 1357–1364 (2012)Cite this article

Abstract

Background

Although the importance of cancer stem cells (CSCs) in overcoming resistance to therapy and metastasis has recently been reported, the role of CSCs in gastric cancer remains to be elucidated.

Methods

MKN-1 cells were used to study markers of CSCs in gastric adenosquamous carcinoma, as these cells are suitable for determining multidifferentiation ability. Changes in expression of CD44, CD49f, CD133, and CD71 following 5-fluorouracil (5-FU) treatment were assessed.

Results

After 5-FU treatment, only the CD71− fraction was significantly increased. Investigation of CD71 indicated that the CD71− cell fraction was present in the G1/G0 cell cycle phase and showed high resistance to the anticancer agent 5-FU. Limiting dilution and serial transplantation assays revealed the CD71− cell fraction to have higher tumorigenicity than the CD71+ cell fraction. The CD71− cell fraction showed multipotency to adenocarcinoma and squamous cell carcinoma. A three-dimensional (3D) invasion assay and immunohistochemical analysis showed CD71− cells to be highly invasive and to exist in the invasive fronts of cancer foci.

Conclusion

The present study suggests that use of CD71− as a marker for adenosquamous carcinoma may provide a useful model for studying CSCs.

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Acknowledgment

We thank T. Shimooka for excellent technical assistance. This work was supported in part by a grant from Core Research for Evolutional Science and Technology, and grants-in-aid for scientific research on priority areas (20012039) and for scientific research (S) (21229015) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Disclosure

There is no conflict of interest.

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Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

    Masahisa Ohkuma MD, Naotsugu Haraguchi MD, PhD, Hideshi Ishii MD, PhD, Ho Min Kim MD, Miho Shimomura MD, Hajime Hirose MD & Masaki Mori MD, PhD

  2. Department of Surgery, Jikei University School of Medicine, Tokyo, Japan

    Masahisa Ohkuma MD & Katsuhiko Yanaga MD, PhD

  3. Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Oita, Japan

    Hideshi Ishii MD, PhD, Koshi Mimori MD, PhD & Fumiaki Tanaka MD, PhD

Authors
  1. Masahisa Ohkuma MD
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  2. Naotsugu Haraguchi MD, PhD
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  3. Hideshi Ishii MD, PhD
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  4. Koshi Mimori MD, PhD
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  5. Fumiaki Tanaka MD, PhD
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  6. Ho Min Kim MD
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  7. Miho Shimomura MD
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  8. Hajime Hirose MD
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  9. Katsuhiko Yanaga MD, PhD
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  10. Masaki Mori MD, PhD
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Corresponding authors

Correspondence to Hideshi Ishii MD, PhD or Masaki Mori MD, PhD.

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Ohkuma, M., Haraguchi, N., Ishii, H. et al. Absence of CD71 Transferrin Receptor Characterizes Human Gastric Adenosquamous Carcinoma Stem Cells. Ann Surg Oncol 19, 1357–1364 (2012). https://doi.org/10.1245/s10434-011-1739-7

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  • DOI: https://doi.org/10.1245/s10434-011-1739-7

Keywords

  • Cell Fraction
  • Side Population
  • Cell Cycle Phase
  • Invasive Front
  • Adenosquamous Carcinoma