Perivascular invasion of primary human glioblastoma cells in organotypic human brain slices: human cells migrating in human brain

Introduction Glioblastoma (GBM) is an aggressive primary brain cancer. Lack of effective therapy is related to its highly invasive nature. GBM invasion has been studied with reductionist systems that do not fully recapitulate the cytoarchitecture of the brain. We describe a human-derived brain organ...

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Bibliographic Details
Published in:Journal of neuro-oncology 2023-08, Vol.164 (1), p.43-54
Main Authors: Ravin, Rea, Suarez-Meade, Paola, Busse, Brad, Blank, Paul S., Vivas-Buitrago, Tito, Norton, Emily S., Graepel, Steve, Chaichana, Kaisorn L., Bezrukov, Ludmila, Guerrero-Cazares, Hugo, Zimmerberg, Joshua, Quiñones-Hinojosa, Alfredo
Format: Article
Language:English
Subjects:
Anoxia
Blood vessels
Brain
Brain architecture
Brain cancer
Brain slice preparation
Brain tumors
Cell culture
Cell migration
Glioblastoma
Glioblastoma cells
Green fluorescent protein
Hypoxia
Immunohistochemistry
Localization
Medicine
Medicine & Public Health
Microenvironments
Neurology
Oncology
Oxygen tension
Surgery
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Summary:Introduction Glioblastoma (GBM) is an aggressive primary brain cancer. Lack of effective therapy is related to its highly invasive nature. GBM invasion has been studied with reductionist systems that do not fully recapitulate the cytoarchitecture of the brain. We describe a human-derived brain organotypic model to study the migratory properties of GBM IDH-wild type ex vivo. Methods Non-tumor brain samples were obtained from patients undergoing surgery (n = 7). Organotypic brain slices were prepared, and green fluorescent protein (GFP)-labeled primary human GBM IDH-wild type cells (GBM276, GBM612, GBM965) were placed on the organotypic slice. Migration was evaluated via microscopy and immunohistochemistry. Results After placement, cells migrated towards blood vessels; initially migrating with limited directionality, sending processes in different directions, and increasing their speed upon contact with the vessel. Once merged, migration speed decreased and continued to decrease with time (p 
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-023-04349-9