Understanding glioblastoma stromal barriers against NK cell attack using tri-culture 3D spheroid model

© 2024 The Authors..

Glioblastoma multiforme (GBM), a highly aggressive tumor type with a dismal survival rate, has a poor outcome which is at least partly attributed to the crosstalk between cancer cells and cells from the tumor microenvironment such as astrocytes and microglia. We aimed to decipher the effect of these cells on GBM progression and on cell-based therapies using 3D co-cultures. Co-culturing of glioblastoma cells with patient-derived astrocytes or microglia or both formed dense and heterogeneous spheroids. Both, astrocytes and microglia, enhanced the spheroid growth rate and formed a physical barrier for macromolecules penetration, while only astrocytes enhanced the migration. Interestingly bi-/tri-cultured spheroids showed significant resistance against NK-92 cells, likely attributed to dense stroma and induced expression of immunosuppressive genes such as IDO1 or PTGES2. Altogether, our novel 3D GBM spheroid model recapitulates the cell-to-cell interactions of human glioblastoma and can serve as a suitable platform for evaluating cancer therapeutics.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Heliyon - 10(2024), 3 vom: 15. Feb., Seite e24808

Sprache:

Englisch

Beteiligte Personen:

Heinrich, Marcel Alexander [VerfasserIn]
Huynh, Ngoc-Tien [VerfasserIn]
Heinrich, Lena [VerfasserIn]
Prakash, Jai [VerfasserIn]

Links:

Volltext

Themen:

3D GBM spheroids
Astrocytes
Chemotherapy
Glioblastoma multiforme
Immunotherapy
Journal Article
Microglia
Natural-killer cells

Anmerkungen:

Date Revised 07.02.2024

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1016/j.heliyon.2024.e24808

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368072355