title: Isolation of head and neck squamous carcinoma cancer stem-like cells             in a syngeneic mouse model and analysis of hypoxia effect.
abstract: The incidence of oral tumors is increasing around the world and despite             recent advances in early detection and diagnosis, current treatments are still             unsatisfactory. Recent data suggest that tumor persistence and recurrence could             be due to the presence of a rare cell population called cancer stem cells (CSCs),             which are generally spared by traditional treatments. Therefore, identification             and characterization of CSCs are extremely important to develop novel and effective             treatment strategies for cancer. The aim of this study was to identify and isolate             CSCs in an established murine head and neck squamous cell carcinoma (HNSCC) cell             line and to investigate the influence of hypoxic conditions on the isolated cell             popul-ation. Using the expression of the aldehyde dehydrogenase 1 (ALDH1) enzymatic             activity, which is now recognized as a CSC marker in various tumors, we isolated             a cell population expressing high levels of ALDH1 (ALDH1high) representing 1±0.6%             in the murine SCC-VII cell line. These cells were injected subcutaneously in syngeneic             animals to evaluate their tumorigenic properties. For the lowest injected cell             dose (250 injected cells), tumor occurrence and median tumor size were higher             in ALDH1high injected mice than in ALDH1low injected mice. Following an in vivo             passage and culture in serum-free medium, the percentage of ALDH1high cells increased             by 3‑fold in SCC-VII CSCs (oral spheres) compared to the SCC-VII cell line. This             percentage was further increased when oral spheres were cultured under hypoxic             conditions. In conclusion, this study reports for the first time the isolation             of HNSCC CSCs in a syngeneic mouse model and the use of hypoxia as a method to             further enrich the ALDH1high cell population.
authors: CNC-Center for Neuroscience and Cell Biology, Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: Sónia
authors: S
authors: Duarte
authors: Agnès
authors: A
authors: Loubat
authors: David
authors: D
authors: Momier
authors: Majlinda
authors: M
authors: Topi
authors: Henrique
authors: H
authors: Faneca
authors: Maria C
authors: MC
authors: Pedroso de Lima
authors: Georges F
authors: GF
authors: Carle
authors: Valérie
authors: V
authors: Pierrefite-Carle
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000473:pathology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000201:enzymology; D014185:Transplantation, Isogeneic; D047368:Tumor Burden
chemical_list: D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase