title: Identification of molecular signature of head and neck cancer stem-like cells.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world. HNSCC remains difficult to treat, and despite advances in treatment, overall survival rate has modestly improved over the past several years. Poor survival rate is attributed to high frequency of local recurrence and distant metastasis. Cancer stem-like cells (CSCs) have been implicated in tumor recurrence and confer resistance to anti-cancer therapy treatment. In this study, we have characterized genes that are modulated in HNSCC-CSCs and can be targeted in future as potential therapeutics. CSCs were isolated from HNSCC cells (oralspheres) and examined for tumorigenicity in immunodeficient mice. We observed aggressive tumor growth with oralspheres as compared to parental cells. The CSC-derived tumors were grossly extremely vascularized and expressed VEGFR1. We next analyzed the molecular determinant of oralspheres. In addition to CD133 and Nanog, we observed significant higher expression of Notch1 protein in the oralspheres. There was differential expression of angiogenesis and invasive marker genes such as angiopoietin1, integrin β3, MMP9 and THBS1. Interestingly, c-Fos was upregulated in oralspheres as compared to parental cells. Our observations suggest that understanding the molecular determinant of oralspheres will help in developing future therapeutic modalities against treatment resistant HNSCC.
authors.affiliation: Department of Pathology, Saint Louis University, Missouri 63104.
authors.forename: Shubham
authors.initials: S
authors.lastname: Shrivastava
authors.affiliation: Department of Pathology, Saint Louis University, Missouri 63104.
authors.forename: Robert
authors.initials: R
authors.lastname: Steele
authors.affiliation: Department of Pathology, Saint Louis University, Missouri 63104.
authors.forename: Melanie
authors.initials: M
authors.lastname: Sowadski
authors.affiliation: 1] Department of Pathology, Saint Louis University, Missouri 63104 [2] Saint Louis University Cancer Center, Saint Louis University, Missouri 63104.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Crawford
authors.affiliation: Saint Louis University Cancer Center, Saint Louis University, Missouri 63104.
authors.forename: Mark
authors.initials: M
authors.lastname: Varvares
authors.affiliation: 1] Department of Pathology, Saint Louis University, Missouri 63104 [2] Saint Louis University Cancer Center, Saint Louis University, Missouri 63104.
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051881:Receptor, Notch1 / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous; D015854:Up-Regulation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D051881:Receptor, Notch1; D040281:Vascular Endothelial Growth Factor Receptor-1