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PLoS One ; 8(4): e62002, 2013.
Article in English | MEDLINE | ID: mdl-23626764

ABSTRACT

Cancer stem cells contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. Here, we report that the CD271(+) population sorted from xenotransplanted HPCs possesses an enhanced tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271(+) cells contained both CD271(+) and CD271(-) cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271(+) cells localized to a perivascular niche near CD34(+) vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metalloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271(+) compared to the CD271 (-) cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Taken together, our findings indicate that CD271 is a novel marker for HPC stem-like cells and for HPC prognosis.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , Hypopharyngeal Neoplasms/genetics , Hypopharynx/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Receptors, Nerve Growth Factor/genetics , Animals , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cisplatin/pharmacology , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Hypopharyngeal Neoplasms/metabolism , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharynx/pathology , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Nanog Homeobox Protein , Neoplasm Staging , Neoplasm Transplantation , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/metabolism , Receptors, Nerve Growth Factor/metabolism , Survival Analysis , Transplantation, Heterologous , Tumor Cells, Cultured
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