BACKGROUND: Molecular profile of @entity463 multiforme (GBM) revealed 4 subtypes, 2 of which, proneural and mesenchymal, have been predominantly observed, with the latter displaying a more @entity146 phenotype and increased therapeutic resistance. Single-cell RNA sequencing revealed that multiple subtypes actually reside within the same @entity5 , suggesting cellular heterogeneity in GBM. Further, plasticity between these 2 subtypes is observed during @entity5 recurrence and in response to radiation therapy. METHODS: @entity1 -derived GBM stemlike cells were cultured as neurospheres. These cells were differentiated in serum by attaching to the culture dishes. The "floating" cells that were not attached/differentiated were harvested from the conditioned medium. The characteristics of these cells were studied with limiting dilution assays and immunofluorescence staining. Cell growth and nuclear factor-kappaB (NFkB) activation were monitored using bioluminescent assays as well as quantitative polymerase chain reaction and western blotting. In vivo tumorigenesis was evaluated in orthotopic xenograft models using bioluminescence imaging. RESULTS: @entity1 -derived GBM stemlike cells undergo differentiation by attaching to the culture dish in serum-containing medium. We observed that a small subset of these cells escape this adhesion/differentiation and grow as floating cells. These cells displayed enhanced @entity5 stem cell properties with a molecular and phenotypic mesenchymal signature, including resistance to radiation and targeted therapies, a more @entity146 @entity5 formation, and NFkB activation. CONCLUSION: Our results endorse inherent intratumor molecular subtype heterogeneity in @entity463 and provide a valuable approach to study phenotypic plasticity, which could be applied to find novel therapeutic strategies to eradicate this @entity146 @entity5 and can be extended to other @entity5 types.

Dissecting inherent intratumor heterogeneity in @entity1 -derived XXXX culture models.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity1 :: ('9606', 'Species') :: ['Patient'] @entity463 :: ('MESH:D005909', 'Disease') :: ['glioblastoma'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive']
@entity463 :: (MESH:D005909,Disease) :: ['glioblastoma']
