CD271 defines a stem cell-like population in hypopharyngeal cancer

Takayuki Imai; Keiichi Tamai; Sayuri Oizumi; Kyoko Oyama; Kazunori Yamaguchi; Ikuro Sato; Kennichi Satoh; Kazuto Matsuura; Shigeru Saijo; Kazuo Sugamura; Nobuyuki Tanaka

doi:10.1371/journal.pone.0062002

CD271 defines a stem cell-like population in hypopharyngeal cancer

PLoS One. 2013 Apr 23;8(4):e62002. doi: 10.1371/journal.pone.0062002. Print 2013.

Authors

Takayuki Imai¹, Keiichi Tamai, Sayuri Oizumi, Kyoko Oyama, Kazunori Yamaguchi, Ikuro Sato, Kennichi Satoh, Kazuto Matsuura, Shigeru Saijo, Kazuo Sugamura, Nobuyuki Tanaka

Affiliation

¹ Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan.

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.

Publication types

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

MeSH terms

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

Substances

Antineoplastic Agents
Biomarkers, Tumor
Homeodomain Proteins
NANOG protein, human
NGFR protein, human
Nanog Homeobox Protein
Nerve Tissue Proteins
Receptors, Nerve Growth Factor
Matrix Metalloproteinases
Cisplatin

Grants and funding

This work was supported by JSPS KAKENHI grant numbers 24300326, 21791589, 24592613, JST CREST, and grants-in-aid from the Ministry of Health, Labour and Welfare, and Takeda Medical foundation, the Ichiro Kanehara foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.