Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma

Nur Rahadiani, Jun Ichiro Ikeda, Tomoki Makino, Tian Tian, Ying Qiu, Suhana Mamat, Yi Wang, Yuichiro Doki, Katsuyuki Aozasa, Eiichi Morii

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1311-1323
Number of pages13
JournalAnnals of Surgical Oncology
Volume17
Issue number5
DOIs
Publication statusPublished - 1 May 2010

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