Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue.

Autor: Harwood DSL; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. dylan.scott.lykke.harwood@regionh.dk.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. dylan.scott.lykke.harwood@regionh.dk., Pedersen V; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Bager NS; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Schmidt AY; Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Stannius TO; Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Areškevičiūtė A; Danish Reference Center for Prion Diseases, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Josefsen K; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Nørøxe DS; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Scheie D; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Rostalski H; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Lü MJS; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark., Locallo A; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark., Lassen U; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Bagger FO; Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Weischenfeldt J; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark., Heiland DH; Department of Neurosurgery, Medical Center-University of Freiburg, Freiburg, Germany.; Microenvironment and Immunology Research Laboratory, Medical Center-University of Freiburg, Freiburg, Germany.; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, USA.; German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany., Vitting-Seerup K; Section for Bioinformatics, Health Technology, Technical University of Denmark (DTU), Kongens Lyngby, Denmark., Michaelsen SR; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Kristensen BW; Department of Clinical Medicine and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. bjarne.winther.kristensen.01@regionh.dk.; The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bjarne.winther.kristensen.01@regionh.dk.; DCCC Brain Tumor Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bjarne.winther.kristensen.01@regionh.dk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 09; Vol. 15 (1), pp. 7857. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1038/s41467-024-52167-y
Abstrakt: Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection.
(© 2024. The Author(s).)
Databáze: MEDLINE
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