Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

Autor: Veronika Fedorova, Veronika Pospisilova, Tereza Vanova, Katerina Amruz Cerna, Pavel Abaffy, Jiri Sedmik, Jan Raska, Simona Vochyanova, Zuzana Matusova, Jana Houserova, Lukas Valihrach, Zdenek Hodny, Dasa Bohaciakova
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Oncology, Vol 17, Iss 4, Pp 647-663 (2023)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13389
Popis: It is currently challenging to adequately model the growth and migration of glioblastoma using two‐dimensional (2D) in vitro culture systems as they quickly lose the original, patient‐specific identity and heterogeneity. However, with the advent of three‐dimensional (3D) cell cultures and human‐induced pluripotent stem cell (iPSC)‐derived cerebral organoids (COs), studies demonstrate that the glioblastoma‐CO (GLICO) coculture model helps to preserve the phenotype of the patient‐specific tissue. Here, we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of cocultured glioblastoma. Our data demonstrate that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model. Lastly, we show that this coculture model (and the human brain‐like microenvironment) can significantly transform the gene expression profile of the established U87 glioblastoma cell line into proneural and classical glioblastoma cell types.
Databáze: Directory of Open Access Journals