Dissecting the role of crosstalk between glioblastoma subpopulations in tumor cell spreading.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
05 Feb 2020
05 Feb 2020
Historique:
received:
02
07
2019
accepted:
24
01
2020
revised:
20
01
2020
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
7
2
2020
Statut:
epublish
Résumé
Glioblastoma (GBM) is a highly infiltrative brain cancer, which is thus difficult to operate. GBM cells frequently harbor Epidermal Growth Factor Receptor amplification (EGFRwt) and/or activating mutation (EGFRvIII), generating at least two different cellular subpopulations within the tumor. We examined the relationship between the diffusive architectures of GBM tumors and the paracrine interactions between those subpopulations. Our aim was to shed light on what drives GBM cells to reach large cell-cell distances, and whether this characteristic can be manipulated. We established a methodology that quantifies the infiltration abilities of cancer cells through computation of cell-cell separation distance distributions in 3D. We found that aggressive EGFRvIII cells modulate the migration and infiltrative properties of EGFRwt cells. EGFRvIII cells secrete HGF and IL6, leading to enhanced activity of Src protein in EGFRwt cells, and rendering EGFRwt cells higher velocity and augmented ability to spread. Src inhibitor, dasatinib, at low non-toxic concentrations, reduced the infiltrative properties of EGFRvIII/EGFRwt neurospheres. Furthermore, dasatinib treatment induced compact multicellular microstructure packing of EGFRvIII/EGFRwt cells, impairing their ability to spread. Prevention of cellular infiltration or induction of compact microstructures may assist the detection of GBM tumors and tumor remnants in the brains and improve their surgical removal.
Identifiants
pubmed: 32024816
doi: 10.1038/s41389-020-0199-y
pii: 10.1038/s41389-020-0199-y
pmc: PMC7002777
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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