Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44

Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew...

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Bibliographic Details
Published in:PloS one 2011-06, Vol.6 (6), p.e21419
Main Authors: Zhao, Jiang-Sha, Li, Wen-Jie, Ge, Di, Zhang, Pei-Jing, Li, Jing-Jing, Lu, Chun-Lai, Ji, Xiao-Dan, Guan, Dong-Xian, Gao, Hong, Xu, Li-Yan, Li, Eng-Ming, Soukiasian, Harmik, Koeffler, H Phillip, Wang, Xiao-Fan, Xie, Dong
Format: Article
Language:English
Subjects:
Acids
Adult
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Assaying
Biochemistry
Biotechnology
Cancer
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - pathology
CD44 antigen
Cell cycle
Cell Death - drug effects
Cell Differentiation - drug effects
Cell Line, Tumor
Colonies
Development and progression
Down-Regulation - drug effects
Drug resistance
Epidermal growth factor
Esophageal cancer
Esophageal carcinoma
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - pathology
Esophagus
Female
Flow cytometry
Gene expression
Genetic aspects
Health aspects
Humans
Hyaluronan Receptors - metabolism
Laboratories
Leukemia
Male
Medicine
Mice
Middle Aged
Molecular biology
Mortality
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - pathology
Oncology
Proteins
Retinoic acid
Rodents
Squamous cell carcinoma
Stem cells
Subpopulations
Surface markers
Surgery
Thoracic surgery
Tumorigenicity
Tumors
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Summary:Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew, as well as, to drive initiation and progression of cancer. Increasing evidence has shown that TICs exist in a variety of tumors. However, the identification and characterization of TICs in esophageal carcinoma has remained elusive. to identify TICs in ESCC, ESCC cell lines including two primary cells were used for screening suitable surface marker. Then colony formation assay, drug resistant assay and tumorigenicity assay in immune deficient mice were used to characterize TICs in ESCC. We found that just the CD44 expression correlated with tumorigenicity in ESCC cell lines. And then induced differentiation of ESCC cells by all-trans retinoic acid treatment led to decreased expression of CD44. The FACS isolated cell subpopulations with high CD44 expression showed increased colony formation and drug resistance in vitro, as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to the low expressing CD44 ESCC cells. our study has discovered a novel TIC surface marker, CD44, which can be utilized to enrich efficiently the TICs in ESCC. These findings will be useful for further studies of these cells and exploring therapeutic approaches.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021419