title: In vitro expansion of human glioblastoma cells at non-physiological             oxygen tension irreversibly alters subsequent in vivo aggressiveness and AC133             expression.
abstract: Among markers of glioblastoma initiating cells, AC133 has been shown to             be associated with glioblastoma resistance and malignancy. Recently, it was demonstrated             that increasing oxygen tension (pO2) down-regulated AC133 expression in glioblastoma             cells in vitro. In order to better understand extrinsic factor regulation of AC133,             this work aimed to investigate the relationship between cell culture pO2, AC133             expression, and tumor development and phenotype. Using treatments with CoCl2 and             HIF-1α shRNA knockdowns on non-sorted human primary glioblastoma cells cultured             at low (3%) versus high (21%) oxygen tension, we established a responsibility             for low pO2 in the maintenance of high levels of AC133 expression, with a major             but non-exclusive role for HIF-1α. We also demonstrated that human glioblastoma             cells previously cultured under high oxygen tension can lose part of their aggressiveness             when orthotopically engrafted in SCID mice or lead to tumors with distinct phenotypes             and no re-expression of AC133. These observations showed that the specific pO2             microenvironment irreversibly impacts glioblastoma cell phenotypes, highlighting             the pertinence of culture conditions when extrapolating data from xenogenic models             to human cells in their source environment. They also raised AC133 as a marker             of non-exposure to oxygenated areas rather than a marker of aggressiveness or             low pO2 niches.
authors: Laboratoire d'Ingénierie de la Vectorisation Particulaire, Inserm,                     UMR_S 646, Université d'Angers, Angers, France.
authors: Erika
authors: E
authors: Bourseau-Guilmain
authors: Laurent
authors: L
authors: Lemaire
authors: Audrey
authors: A
authors: Griveau
authors: Eric
authors: E
authors: Hervouet
authors: François
authors: F
authors: Vallette
authors: François
authors: F
authors: Berger
authors: Philippe
authors: P
authors: Menei
authors: Jean-Pierre
authors: JP
authors: Benoit
authors: Didier
authors: D
authors: Wion
authors: Emmanuel
authors: E
authors: Garcion
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D010100:Oxygen / Q000008:administration & dosage*; D010313:Partial Pressure; D010455:Peptides / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D010100:Oxygen