Original Article

Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells

  1. Kazuaki Chikamatsu MD, PhD1,*,
  2. Hiroki Ishii MD1,
  3. Goro Takahashi MD, PhD1,2,
  4. Atsushi Okamoto MD, PhD1,
  5. Motohiro Moriyama MD1,
  6. Koichi Sakakura MD, PhD3,
  7. Keisuke Masuyama MD, PhD1

Article first published online: 5 APR 2011

DOI: 10.1002/hed.21732

Issue

Head & Neck

Head & Neck

Volume 34, Issue 3, pages 336–343, March 2012

Additional Information

How to Cite

Chikamatsu, K., Ishii, H., Takahashi, G., Okamoto, A., Moriyama, M., Sakakura, K. and Masuyama, K. (2012), Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells. Head Neck, 34: 336–343. doi: 10.1002/hed.21732

Author Information

  1. 1

    Department of Otolaryngology–Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, 409-3898, Japan

  2. 2

    Department of Otolaryngology, Hamamatsu University School of Medicine, Shizuoka, Japan

  3. 3

    Department of Otolaryngology–Head and Neck Surgery, National Hospital Organization Shizuoka Medical Center, Shizuoka, Japan

*Department of Otolaryngology–Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, 409-3898, Japan

Publication History

  1. Issue published online: 7 FEB 2012
  2. Article first published online: 5 APR 2011
  3. Manuscript Accepted: 22 DEC 2010
  4. Manuscript Revised: 25 NOV 2010
  5. Manuscript Received: 10 AUG 2010

Funded by

  • Ministry of Education, Cultures, Sports, Science, and Technology of Japan. Grant Numbers: 20592013, 20592014

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Keywords:

  • cancer stem cells;
  • apoptosis;
  • CD44;
  • head and neck squamous cell carcinoma;
  • treatment resistance

Abstract

Background

CD44 was identified previously as a surface marker in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). Most cancer treatments have been linked to the activation of the apoptosis-signaling pathway; however, the resistance mechanisms to apoptosis in CSCs have not yet been fully elucidated.

Methods

The sensitivity of CD44+ cells to diverse apoptosis-inducing stimuli was compared with that of CD44- cells. Furthermore, cell cycle changes and the expression of anti-apoptosis-related genes were examined using flow cytometry and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).

Results

CD44+ cells were resistant to various apoptosis-inducing stimuli. Moreover, CD44+ cells showed a higher proportion of cells in G2/M phase of the cell cycle and upregulation of Bcl-2 and inhibitor of apoptosis (IAP) family genes compared with CD44- cells.

Conclusion

Treatment resistance in CSCs seems to be regulated by various mechanisms, and, therefore, additional treatment strategies to target CSCs are required in patients with HNSCC. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

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