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In vitro expansion of human glioblastoma cells at non-physiological oxygen tension irreversibly alters subsequent in vivo aggresiveness and AC 133 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.
https://hal.univ-angers.fr/hal-03165456
Contributeur : Okina Université d'Angers <>
Soumis le : mercredi 10 mars 2021 - 16:30:32
Dernière modification le : vendredi 21 mai 2021 - 11:56:01
Archivage à long terme le : : vendredi 11 juin 2021 - 19:12:01
Contributeur : Okina Université d'Angers <>
Soumis le : mercredi 10 mars 2021 - 16:30:32
Dernière modification le : vendredi 21 mai 2021 - 11:56:01
Archivage à long terme le : : vendredi 11 juin 2021 - 19:12:01
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