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International Journal of Oncology
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Article

p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma

  • Authors:
    • Tetsuji Yamaguchi
    • Tomoyuki Okumura
    • Katsuhisa Hirano
    • Toru Watanabe
    • Takuya Nagata
    • Yutaka Shimada
    • Kazuhiro Tsukada
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama City, Toyama 930-0194, Japan, Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
  • Pages: 1943-1954
    |
    Published online on: March 10, 2016
       https://doi.org/10.3892/ijo.2016.3432
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Abstract

Mitotically quiescent cancer stem cells (CSC) are hypothesized to exhibit a more aggressive phenotype involving greater therapeutic resistance and metastasis. The aim of our study was to develop a method for identifying quiescent CSC in esophageal squamous cell carcinoma (ESCC) based on their expression of the p75 neurotrophin receptor (p75NTR) and other proposed CSC markers, such as CD44 and CD90. Double immunostaining of surgical ESCC specimens revealed that the mean Ki-67-labeling index of the p75NTR-positive cells was significantly lower than that of the p75NTR-negative cells. Real-time PCR analysis of sorted fractions of ESCC cell lines (KYSE cells) revealed that stem cell-related genes (Nanog, p63 and Bmi-1) and epithelial-mesenchymal transition (EMT)-related genes (N-cadherin and fibronectin) were expressed at significantly higher levels in the p75NTR-positive fractions than in the CD44-positive or CD90-positive fractions. In addition, the p75NTR-positive fractions exhibited significantly higher colony formation in vitro, significantly enhanced tumor formation in mice, and significantly greater chemoresistance against cisplatin (CDDP) than the CD44‑positive or CD90‑positive fractions. Furthermore, in both the cultured cells and those from the mouse xenograft tumors, the p75NTR‑positive/CD44-negative and p75NTR‑positive/CD90-negative KYSE cell fractions contained significantly higher proportions of mitotically quiescent cells. These results suggest that the mitotically quiescent CSC population in ESCC can be identified and isolated based on their p75NTR expression, providing researchers with a novel diagnostic and therapeutic target.
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Copy and paste a formatted citation
Spandidos Publications style
Yamaguchi T, Okumura T, Hirano K, Watanabe T, Nagata T, Shimada Y and Tsukada K: p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma. Int J Oncol 48: 1943-1954, 2016.
APA
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., & Tsukada, K. (2016). p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma. International Journal of Oncology, 48, 1943-1954. https://doi.org/10.3892/ijo.2016.3432
MLA
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., Tsukada, K."p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma". International Journal of Oncology 48.5 (2016): 1943-1954.
Chicago
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., Tsukada, K."p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma". International Journal of Oncology 48, no. 5 (2016): 1943-1954. https://doi.org/10.3892/ijo.2016.3432
Copy and paste a formatted citation
x
Spandidos Publications style
Yamaguchi T, Okumura T, Hirano K, Watanabe T, Nagata T, Shimada Y and Tsukada K: p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma. Int J Oncol 48: 1943-1954, 2016.
APA
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., & Tsukada, K. (2016). p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma. International Journal of Oncology, 48, 1943-1954. https://doi.org/10.3892/ijo.2016.3432
MLA
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., Tsukada, K."p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma". International Journal of Oncology 48.5 (2016): 1943-1954.
Chicago
Yamaguchi, T., Okumura, T., Hirano, K., Watanabe, T., Nagata, T., Shimada, Y., Tsukada, K."p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma". International Journal of Oncology 48, no. 5 (2016): 1943-1954. https://doi.org/10.3892/ijo.2016.3432
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