RRC ID 38215
Author Rahadiani N, Ikeda J, Makino T, Tian T, Qiu Y, Mamat S, Wang Y, Doki Y, Aozasa K, Morii E.
Title Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma.
Journal Ann. Surg. Oncol.
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.
Volume 17(5)
Pages 1311-23
Published 2010-5
DOI 10.1245/s10434-009-0895-5
PMID 20066519
MeSH Aged Aged, 80 and over Animals Antineoplastic Agents / pharmacology Apoptosis / drug effects Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Blotting, Western Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Movement Cell Proliferation / drug effects Colony-Forming Units Assay Esophageal Neoplasms / drug therapy Esophageal Neoplasms / metabolism* Esophageal Neoplasms / pathology Female Flow Cytometry Gene Silencing / physiology Humans Immunoenzyme Techniques Male Membrane Glycoproteins / physiology* Mice Mice, Inbred NOD Mice, SCID Middle Aged RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / pharmacology Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tissue Array Analysis Topotecan / pharmacology Treatment Outcome Tumor Cells, Cultured Xenograft Model Antitumor Assays
IF 3.681
Times Cited 42
Human and Animal Cells