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Tumorigenic Role of Podoplanin in Esophageal Squamous-Cell Carcinoma

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Podoplanin, a mucin-type transmembrane glycoprotein, is thought to be one of the cancer stem cell markers for squamous-cell carcinoma of the vulva. The objectives of the present study were to examine the role of podoplanin in esophageal squamous-cell carcinoma (ESCC).

Methods

Expression of podoplanin was examined immunohistochemically in 61 cases of ESCC that had not been treated with chemotherapy or radiotherapy before surgery. Because cancer stem-cell quantities have been reported to increase with chemotherapy and radiotherapy, cases in patients who did not receive such prior therapies were included in this study. Cases with >10% tumor cells showing signals for podoplanin were categorized as podoplanin high, and the others were classified as podoplanin low. The effects of podoplanin on the behavior of cancer cells were evaluated in ESCC cell lines in which podoplanin expression was knocked down.

Results

To examine whether podoplanin could be used as a cancer stem cell marker for ESCC, podoplanin-positive and podoplanin-negative fractions were sorted separately from the ESCC cell line and cultured. Podoplanin-positive ESCC cells yielded both podoplanin-positive and podoplanin-negative cells, whereas few cells were obtained from podoplanin-negative ESCC cells. When podoplanin expression was knocked down, ESCC cell lines became vulnerable to anticancer drugs and showed defective invasion and tumorigenic activities. Nineteen (31.1%) of 61 cases were categorized as podoplanin high. Podoplanin-high cases were correlated with T category, stage of disease, lymphatic and vascular invasion, recurrence, and prognosis of patients. Podoplanin-low cases showed better overall and disease-free survival.

Conclusions

There is a role for podoplanin in tumorigenesis and malignant progression in ESCC.

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Acknowledgment

We thank Masaharu Kohara, Megumi Sugano, Etsuko Maeno, and Takako Sawamura for their technical assistance. There is no conflict of interest in this study. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (grants 20590364 and 20014010).

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Authors and Affiliations

  1. Department of Pathology, Osaka University, Graduate School of Medicine, Osaka, Japan

    Nur Rahadiani MD, Jun-ichiro Ikeda MD, Tian Tian MD, Ying Qiu MD, Suhana Mamat BSc, Yi Wang MD, Katsuyuki Aozasa MD & Eiichi Morii MD

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

    Tomoki Makino MD & Yuichiro Doki MD

  3. Department of Pathology, Tongi University School of Medicine, Shanghai, China

    Ying Qiu MD

  4. Department of Basic Health Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Pahang, Malaysia

    Suhana Mamat BSc

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  1. Nur Rahadiani MD
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  2. Jun-ichiro Ikeda MD
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Correspondence to Eiichi Morii MD.

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Rahadiani, N., Ikeda, Ji., Makino, T. et al. Tumorigenic Role of Podoplanin in Esophageal Squamous-Cell Carcinoma. Ann Surg Oncol 17, 1311–1323 (2010). https://doi.org/10.1245/s10434-009-0895-5

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  • DOI: https://doi.org/10.1245/s10434-009-0895-5

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