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2023, Volume 39, Number 2, Page(s) 117-132     
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DOI: 10.5146/tjpath.2022.01582
Development of Glioblastoma from Stem Cells to a Full-Fledged Tumor
Pavel Vladimirovich NIKITIN1, Guzel Railevna MUSINA2, Valery Nikolaevich POLOZOV3, Dmitry Nikolaevich GOREIKO4, Vladimir Mikhailovich KRASNOVSKY5, Leonard WERKENBARK6, Mauric KJELIN7, Piotr Sergeevich TIMASHEV1,8,9
1Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, MOSCOW, RUSSIA
2Federal Center for Brain and Neurotechnologies, MOSCOW, RUSSIA
3A.A. Bogomolets National Medical University, KYIV, UKRAINE
4Kharkiv National Medical University, KHARKIV, UKRAINE
5N.N. Blokhin Cancer Research Center, MOSCOW, RUSSIA
6University of Brussels, BRUSSELS, BELGIUM
7University of Bordeaux, BORDEAUX, FRANCE
8Chemistry Department, Lomonosov Moscow State University, MOSCOW, RUSSIA
9World-Class Research Center “Digital biodesign and personalized healthcare,” Sechenov First Moscow State Medical University, MOSCOW, RUSSIA
Keywords: Glioblastoma, Carcinogenesis, Intratumoral heterogeneity, Glioma stem cells, Tumor evolution

Objective: IDH wild-type glioblastomas (GBM) are one of the most malignant and complex tumors for treatment. The urgent question of new therapeutic and diagnostic tools searching should be resolved based on cellular and molecular pathogenesis mechanisms, which remain insufficiently studied. In this study, we aimed to investigate GBM pathogenesis.

Material and Method:/b> Using the isolation of different GBM cell populations and the cell cultures, animal models, and molecular genetic methods, we tried to clarify the picture of GBM pathogenesis by constructing a projection from different glioma stem cells types to an integral neoplasm.

Results: We have shown a potential transformation pathway for both glioma stem cells and four definitive cell populations during gliomagenesis. Moreover, we have characterized each population, taking into account its place in the pathogenetic continuum, with a description of the most fundamental molecular and functional properties.

Conclusion: Finally, we have formed a complex holistic concept of the pathogenetic evolution of GBM at the cell-population level by integrating our results with the data of the world literature.

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