Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas

Journal Article · Sat Oct 15 04:00:00 EDT 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.09.003· OSTI ID:22649772

Kaseb, Hatem O. ^[1]; Fohrer-Ting, Helene ^[2]; Lewis, Dale W. ^[1]; Lagasse, Eric ^[2]

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1. Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261 (United States)
2. Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 (United States)

Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. Recent data indicate the presence of cancer stem cells (CSC) in many solid tumors, including HNSCC. Here, we assessed the stem cell (SC) characteristics, including cell surface markers, radioresistance, chromosomal instability, and in vivo tumorigenic capacity of CSC isolated from HNSCC patient specimens. We show that spheroid enrichment of CSC from early and short-term HNSCC cell cultures was associated with increased expression of CD44, CD133, SOX2 and BMI1 compared with normal oral epithelial cells. On immunophenotyping, five of 12 SC/CSC markers were homogenously expressed in all tumor cultures, while one of 12 was negative, four of 12 showed variable expression, and two of the 12 were expressed heterogeneously. We showed that irradiated CSCs survived and retained their self-renewal capacity across different ionizing radiation (IR) regimens. Fluorescence in situ hybridization (FISH) analyses of parental and clonally-derived tumor cells revealed different chromosome copy numbers from cell to cell, suggesting the presence of chromosomal instability in HNSCC CSC. Further, our in vitro and in vivo mouse engraftment studies suggest that CD44+/CD66− is a promising, consistent biomarker combination for HNSCC CSC. Overall, our findings add further evidence to the proposed role of HNSCC CSCs in therapeutic resistance. - Highlights: • Spheroid enrichment selects cancer stem cells (CSC) from head & neck tumors (HNSCC). • Compared to normal epithelial cells, isolated CSC express increased SC/CSC markers. • Isolated CSC display enhanced radioresistance, clonogenicity and tumorigenicity. • HNSCC CSC express chromosomal instability. • CD44+/CD66− is a promising, consistent biomarker for HNSCC CSC.

• OSTI ID: 22649772
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 348; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL MARKERS
CARCINOMAS
CELL CULTURES
CHROMOSOMES
COMPARATIVE EVALUATIONS
DILUTION
EFFICIENCY
FLUORESCENCE
HEAD
IN VITRO
IN VIVO
INSTABILITY
IONIZING RADIATIONS
IRRADIATION
LUNGS
MICE
NECK
PATIENTS
PUBLIC HEALTH
RADIOSENSITIVITY
SOLIDS
SPHEROIDS
STEM CELLS
TUMOR CELLS