Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma

Chun-Hung Yang; Hui-Ling Wang; Yi-Sheng Lin; K P Shravan Kumar; Hung-Chi Lin; Chih-Jung Chang; Chia-Chen Lu; Tsung-Teng Huang; Jan Martel; David M Ojcius; Yu-Sun Chang; John D Young; Hsin-Chih Lai

doi:10.1371/journal.pone.0099412

Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma

PLoS One. 2014 Jun 23;9(6):e99412. doi: 10.1371/journal.pone.0099412. eCollection 2014.

Authors

Affiliations

¹ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Division of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, Republic of China.
² Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
³ Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
⁴ Department of Respiratory Therapy, Fu Jen Catholic University, Taipei, Taiwan, Republic of China.
⁵ Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Research Center of Bacterial Pathogenesis, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
⁶ Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
⁷ Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Molecular Cell Biology and Health Sciences Research Institute, University of California Merced, Merced, California, United States of America.
⁸ Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
⁹ Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York, United States of America; Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei, Taiwan, Republic of China.

Abstract

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / metabolism
Animals
Biomarkers, Tumor / metabolism*
CD24 Antigen / metabolism*
Carcinoma
Cell Count
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Cell Separation
Clone Cells
Drug Resistance, Neoplasm
Flow Cytometry
Gene Expression Regulation, Neoplastic
Humans
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Mice, Inbred NOD
Mice, SCID
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / enzymology
Nasopharyngeal Neoplasms / genetics
Nasopharyngeal Neoplasms / metabolism*
Nasopharyngeal Neoplasms / pathology*
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Neoplastic Stem Cells / metabolism*
Spheroids, Cellular / pathology
Wnt Signaling Pathway

Substances

ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Biomarkers, Tumor
CD24 Antigen
CD24 protein, human
Neoplasm Proteins
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9

Grants and funding

This study was supported by grants NSC101-2325-B-182-005 and NSC101-2320-B-030-011 from the National Science Council of Taiwan, and grant CMRPD1B0052 from Chang Gung Memorial Hospital (Linkou, Taiwan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.