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Tumor-specific migration routes of xenotransplanted human glioblastoma cells in mouse brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, article id 864Article in journal (Refereed) Published
Abstract [en]

The migration of neural progenitor cells (NPCs) to their final destination during development follows well-defined pathways, such as along blood vessels. Cells originating from the highly malignant tumor glioblastoma (GBM) seem to exploit similar routes for infiltrating the brain parenchyma. In this report, we have examined the migration of GBM cells using three-dimensional high-resolution confocal microscopy in brain tumors derived from eight different human GBM cell lines xenografted into immunodeficient mice. The primary invasion routes identified were long-distance migration along white matter tracts and local migration along blood vessels. We found that GBM cells in the majority of tumors (6 out of 8) did not exhibit association with blood vessels. These tumors, derived from low lamin A/C expressing GBM cells, were comparatively highly diffusive and invasive. Conversely, in 2 out of 8 tumors, we noted perivascular invasion and displacement of astrocyte end-feet. These tumors exhibited less diffusive migration, grew as solid tumors, and were distinguished by elevated expression of lamin A/C. We conclude that the migration pattern of glioblastoma is distinctly tumor cell-specific. Furthermore, the ability to invade the confined spaces within white matter tracts may necessitate low expression of lamin A/C, contributing to increased nuclear plasticity. This study highlights the role of GBM heterogeneity in driving the aggressive growth of glioblastoma.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 14, article id 864
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Cancer and Oncology Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-522882DOI: 10.1038/s41598-023-51063-7ISI: 001139656300036PubMedID: 38195678OAI: oai:DiVA.org:uu-522882DiVA, id: diva2:1837061
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Swedish Cancer SocietyAvailable from: 2024-02-12 Created: 2024-02-12 Last updated: 2024-02-12Bibliographically approved

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Gupta, Rajesh KumarNiklasson, MiaBergström, TobiasSegerman, AnnaBetsholtz, ChristerWestermark, Bengt

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