Abstract
Tumor-initiating cells (TIC), also known as cancer stem cells, are regarded widely as a specific subpopulation of cells needed for cancer initiation and progression. TICs have yet to be identified in esophageal tumors that have an increasing incidence in developed countries. Here, we report a CD90(+) cell population found in esophageal squamous cell carcinoma (ESCC), which is endowed with stem cell-like properties and high tumorigenic and metastatic potential. mRNA profiling of these cells suggested pathways through which they drive tumor growth and metastasis, with deregulation of an Ets-1/MMP signaling pathway and epithelial-mesenchymal transition figuring prominently. These cells possessed higher self-renewal activity and were sufficient for tumor growth, differentiation, metastasis, and chemotherapeutic resistance. CD90(+) TICs were isolated and characterized from ESCC clinical specimens as well as ESCC cell lines. In freshly resected clinical specimens, they represented a rare cell population, the levels of which correlated with strong family histories and lymph node metastasis. Our results prompt further study of this CD90(+) population of esophageal TICs as potential therapeutic targets.
©2013 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Blotting, Western
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / secondary*
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Cell Adhesion
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Cell Differentiation
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Cell Movement*
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Cell Proliferation*
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Disease Progression
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Epithelial-Mesenchymal Transition*
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Esophageal Neoplasms / genetics
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Esophageal Neoplasms / metabolism
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Esophageal Neoplasms / pathology*
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Female
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Flow Cytometry
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Gene Expression Profiling
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Humans
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Immunoenzyme Techniques
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Liver Neoplasms, Experimental / genetics
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Liver Neoplasms, Experimental / metabolism
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Liver Neoplasms, Experimental / secondary
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / secondary
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Lymphatic Metastasis
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Male
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Middle Aged
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Neoplasm Staging
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Thy-1 Antigens / chemistry
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Thy-1 Antigens / genetics
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Thy-1 Antigens / metabolism*
Substances
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Biomarkers, Tumor
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RNA, Messenger
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RNA, Small Interfering
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Thy-1 Antigens