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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2010

01-05-2010 | Gastrointestinal Oncology

Tumorigenic Role of Podoplanin in Esophageal Squamous-Cell Carcinoma

Authors: Nur Rahadiani, MD, Jun-ichiro Ikeda, MD, Tomoki Makino, MD, Tian Tian, MD, Ying Qiu, MD, Suhana Mamat, BSc, Yi Wang, MD, Yuichiro Doki, MD, Katsuyuki Aozasa, MD, Eiichi Morii, MD

Published in: Annals of Surgical Oncology | Issue 5/2010

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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.
Literature
1.
2.
Hemburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Cell Sci. 1977;197:461–3.
3.
Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature. 1963;199:79–80.CrossRefPubMed
4.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.CrossRefPubMed
5.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.CrossRefPubMed
6.
Lessard J, Sauvageau G. Bmi-1 determined the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423:255–60.CrossRefPubMed
7.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.CrossRefPubMed
8.
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMed
9.
Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.CrossRefPubMed
10.
Fang D, Nguyen TK, Leishear K, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005;65:9328–37.CrossRefPubMed
11.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, at al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;2445:111–5.CrossRef
12.
Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.CrossRefPubMed
13.
Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 2007;104:973–8.CrossRefPubMed
14.
Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008;13:153–66.CrossRefPubMed
15.
Takaishi S, Okumura T, Tu S, et al. Identification of gastric stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–20.CrossRefPubMed
16.
Atsumi N, Ishii G, Kijima M, et al. Podoplanin a novel marker of tumor-initiating cells in human squamous cell carcinoma A431. Biochem Biophys Res Commun. 2008;373:36–41.CrossRefPubMed
17.
Wicki A, Christofori G. The potential role of podoplanin in tumor invasion. Br J Cancer. 2007;96:1–5.CrossRefPubMed
18.
Yuan P, Temam S, El Naggar A, et al. Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer. 2006;107:563–9.CrossRefPubMed
19.
Dumoff KL, Chu C, Xu X, et al. Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in early-stage squamous cell carcinoma of the uterine cervix. Mod Pathol. 2005;18:97–104.CrossRefPubMed
20.
Ito T, Ishii G, Nagai K, et al. Low podoplanin expression of tumor cells predicts poor prognosis in pathological stage IB squamous cell carcinoma of the lung, tissue microarray analysis of 136 patients using 24 antibodies. Lung Cancer. 2009;63:418–24.CrossRefPubMed
21.
Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries 1973–1995. Int J Cancer. 2002;99:860–8.CrossRefPubMed
22.
Morita M, Yoshida R, Ikeda K, et al. Advances in esophageal cancer surgery in Japan: an analysis of 1000 consecutive patients treated at a single institute. Surgery. 2008;143:499–508.CrossRefPubMed
23.
Slichenmyer WJ, Von Hoff DD. New natural products in cancer chemotherapy. J Clin Pharmacol. 1990;30:770–88.PubMed
24.
Tomicic MT, Christmann M, Kaina B. Topotecan-triggered degradation of topoisomerase I is p53-dependent and impacts cell survival. Cancer Res. 2005;65:8920–6.CrossRefPubMed
25.
Meyer-Siegler KL, Iczknowski KA, Leng L, Bucala R, Vera PL. Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol. 2006;177:8730–9.PubMed
26.
Oda T, Tian T, Inoue M, et al. Tumorigenic role of orphan nuclear receptor NR0B1 in lung adenocarcinoma. Am J Pathol. 2009;175:1235–45.CrossRefPubMed
27.
Diehn M, Cho RW, Lobo NA, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009;458:780–3.CrossRefPubMed
28.
Song W, Li H, Tao K, et al. Expression and clinical significance of the stem cell marker CD133 in hepatocellular carcinoma. Int J Clin Pract. 2008;62:1212–8.CrossRefPubMed
29.
Mueller MT, Hermann PC, Witthauer J, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology. 2009;137:1102–12.CrossRefPubMed
30.
Abraham BK, Fritz P, McClellan M, et al. Prevalence of CD44+/CD24−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005;11:1154–9.PubMed
31.
Scholl FG, Gamallo C, Vilaró S, Quintanilla M. Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci. 1999;112:4601–13.PubMed
32.
Wicki A, Lehembre F, Wick N, et al. Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell. 2006;9:261–72.CrossRefPubMed
Metadata
Title
Tumorigenic Role of Podoplanin in Esophageal Squamous-Cell Carcinoma
Authors
Nur Rahadiani, MD
Jun-ichiro Ikeda, MD
Tomoki Makino, MD
Tian Tian, MD
Ying Qiu, MD
Suhana Mamat, BSc
Yi Wang, MD
Yuichiro Doki, MD
Katsuyuki Aozasa, MD
Eiichi Morii, MD
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0895-5

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