Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions
Buehler M, Yi X, Ge W, Blattmann P, Rushing E, Reifenberger G, Felsberg J, Yeh C, Corn JE, Regli L, Zhang J, Cloos A, Ravi VM, Wiestler B, Heiland DH, Aebersold R, Weller M, Guo T, Weiss T (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 25
Pages Range: 290-302
Journal Issue: 2
Abstract
Background: Recent efforts have described the evolution of glioblastoma from initial diagnosis to post-treatment recurrence on a genomic and transcriptomic level. However, the evolution of the proteomic landscape is largely unknown. Methods: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to characterize the quantitative proteomes of two independent cohorts of paired newly diagnosed and recurrent glioblastomas. Recurrence-associated proteins were validated using immunohistochemistry and further studied in human glioma cell lines, orthotopic xenograft models, and human organotypic brain slice cultures. External spatial transcriptomic, single-cell, and bulk RNA sequencing data were analyzed to gain mechanistic insights. Results: Although overall proteomic changes were heterogeneous across patients, we identified BCAS1, INF2, and FBXO2 as consistently upregulated proteins at recurrence and validated these using immunohistochemistry. Knockout of FBXO2 in human glioma cells conferred a strong survival benefit in orthotopic xenograft mouse models and reduced invasive growth in organotypic brain slice cultures. In glioblastoma patient samples, FBXO2 expression was enriched in the tumor infiltration zone and FBXO2-positive cancer cells were associated with synaptic signaling processes. Conclusions: These findings demonstrate a potential role of FBXO2-dependent glioma-microenvironment interactions to promote tumor growth. Furthermore, the published datasets provide a valuable resource for further studies.
Involved external institutions
Universitätsspital Zürich (USZ)
Switzerland (CH)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
Klinikum rechts der Isar
Germany (DE)
Switzerland (CH)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
Heinrich-Heine-Universität Düsseldorf
Germany (DE)
Universitätsklinikum Freiburg
Germany (DE)
Klinikum rechts der Isar
Germany (DE)
How to cite
APA:
Buehler, M., Yi, X., Ge, W., Blattmann, P., Rushing, E., Reifenberger, G.,... Weiss, T. (2023). Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions. Neuro-Oncology, 25(2), 290-302. https://doi.org/10.1093/neuonc/noac169
MLA:
Buehler, Marcel, et al. "Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions." Neuro-Oncology 25.2 (2023): 290-302.
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