PMID- 27619333 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20190221 IS - 1090-2422 (Electronic) IS - 0014-4827 (Print) IS - 0014-4827 (Linking) VI - 348 IP - 1 DP - 2016 Oct 15 TI - Identification, expansion and characterization of cancer cells with stem cell properties from head and neck squamous cell carcinomas. PG - 75-86 LID - 10.1016/j.yexcr.2016.09.003 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Kaseb, Hatem O AU - Kaseb HO AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, 15261, United States of America. AD - Department of Clinical Pathology, National Cancer Institute (NCI), Cairo University, Cairo, Egypt. FAU - Fohrer-Ting, Helene AU - Fohrer-Ting H AD - Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15261, United States of America. AD - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA, 15219, United States of America. FAU - Lewis, Dale W AU - Lewis DW AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, 15261, United States of America. FAU - Lagasse, Eric AU - Lagasse E AD - Department of Pathology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15261, United States of America. AD - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA, 15219, United States of America. FAU - Gollin, Susanne M AU - Gollin SM AD - Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, 15261, United States of America. AD - University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15232, United States of America. LA - eng GR - P30 CA047904/CA/NCI NIH HHS/United States GR - P50 CA097190/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20160909 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Antigens, CD) RN - 0 (Biomarkers, Tumor) SB - IM MH - Aged MH - Aged, 80 and over MH - Animals MH - Antigens, CD/metabolism MH - Biomarkers, Tumor/metabolism MH - Carcinogenesis/pathology MH - Carcinoma, Squamous Cell/metabolism/*pathology MH - Cell Line, Tumor MH - Cell Proliferation MH - Cell Self Renewal MH - Cell Separation MH - Chromosomal Instability MH - Clone Cells MH - Feeder Cells/cytology MH - Female MH - Fluorescent Antibody Technique MH - Head and Neck Neoplasms/metabolism/*pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice MH - Middle Aged MH - Neoplastic Stem Cells/metabolism/*pathology MH - Radiation Tolerance MH - Squamous Cell Carcinoma of Head and Neck PMC - PMC5056028 MID - NIHMS817518 OTO - NOTNLM OT - Cancer stem cells OT - Cell surface markers OT - Chromosomal instability OT - Head and neck squamous cell carcinoma OT - Radioresistance EDAT- 2016/09/14 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/10/15 CRDT- 2016/09/14 06:00 PHST- 2016/04/25 00:00 [received] PHST- 2016/08/15 00:00 [revised] PHST- 2016/09/07 00:00 [accepted] PHST- 2016/09/14 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/09/14 06:00 [entrez] PHST- 2017/10/15 00:00 [pmc-release] AID - 10.1016/j.yexcr.2016.09.003 [doi] PST - ppublish SO - Exp Cell Res. 2016 Oct 15;348(1):75-86. doi: 10.1016/j.yexcr.2016.09.003. Epub 2016 Sep 9.