Tumorigenic Role of Podoplanin in Esophageal Squamous-Cell Carcinoma
- 12 January 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Annals of Surgical Oncology
- Vol. 17 (5), 1311-1323
- https://doi.org/10.1245/s10434-009-0895-5
Abstract
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).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.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.There is a role for podoplanin in tumorigenesis and malignant progression in ESCC.Keywords
This publication has 27 references indexed in Scilit:
- Tumorigenic Role of Orphan Nuclear Receptor NR0B1 in Lung AdenocarcinomaThe American Journal of Pathology, 2009
- Association of reactive oxygen species levels and radioresistance in cancer stem cellsNature, 2009
- Podoplanin, a novel marker of tumor-initiating cells in human squamous cell carcinoma A431Biochemical and Biophysical Research Communications, 2008
- Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinomaProceedings of the National Academy of Sciences of the United States of America, 2007
- The potential role of podoplanin in tumour invasionBritish Journal of Cancer, 2006
- A Tumorigenic Subpopulation with Stem Cell Properties in MelanomasCancer Research, 2005
- Prospective identification of tumorigenic breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2003
- Time trends incidence of both major histologic types of esophageal carcinomas in selected countries, 1973–1995International Journal of Cancer, 2002
- Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cellNature Medicine, 1997
- New Natural Products in Cancer ChemotherapyThe Journal of Clinical Pharmacology, 1990