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Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro

Oncogene volume 22, pages 4017–4026 (2003)Cite this article

Abstract

We report here that human esophageal keratinocyte stem cells are characterized by the expression of the low-affinity neurotrophin receptor p75NTR and differentially expressed cell adhesion molecules, the β1 and β4 integrins. The candidate stem cells could be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. Flow cytometric analysis revealed that this minor cell subset retained a relatively slow-cycling phenotype in vitro. These cells expressed low levels of involucrin and cytokeratin 13, indicating that the p75NTR-positive cell subset is immature relative to the other predominant subpopulations coexpressing β1 integrin at higher levels. The p75NTR-positive cell subset was crucial for achieving longevity and the greatest output of keratinocytes comprising all distinguishable subpopulations in vitro. This process was associated with self-renewal and self-amplification of the p75NTR-positive cell subset. These findings strongly implicate p75NTR as a stem cell marker, which will be valuable for prospectively investigating stem cell regulation in association with different biological processes including neoplastic transformation of regenerative epithelia.

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Acknowledgements

We appreciate the efforts of the clinical staff in providing us with surgically dissected tissue specimens of esophagus from patients who had given informed consent. We are grateful to those patients who were willing to be participants in this study. The authors thank Dr K Kikuchi for helpful advice on flow cytometric analysis. This study was partly supported by a grant-in-aid from the Ministry of Health, Labor and Welfare.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology and Oncology, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan

    Tomoyuki Okumura & Shigeru Yasumoto

  2. Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan

    Tomoyuki Okumura, Yutaka Shimada & Masayuki Imamura

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  1. Tomoyuki Okumura
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  2. Yutaka Shimada
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  4. Shigeru Yasumoto
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Correspondence to Shigeru Yasumoto.

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Okumura, T., Shimada, Y., Imamura, M. et al. Neurotrophin receptor p75NTR characterizes human esophageal keratinocyte stem cells in vitro. Oncogene 22, 4017–4026 (2003). https://doi.org/10.1038/sj.onc.1206525

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