Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells

Introduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic...

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Main Authors: V. E. Shevchenko, Z. N. Nikiforova, T. I. Kushnir, I. A. Kudryavtsev, A. A. Mitrofanov, A. Kh. Bekyashev, N. E. Arnotskaya
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Language:Russian
Published: ABV-press 2022-10-01
Series:Успехи молекулярной онкологии
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Online Access:https://umo.abvpress.ru/jour/article/view/459
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author V. E. Shevchenko
Z. N. Nikiforova
T. I. Kushnir
I. A. Kudryavtsev
A. A. Mitrofanov
A. Kh. Bekyashev
N. E. Arnotskaya
author_facet V. E. Shevchenko
Z. N. Nikiforova
T. I. Kushnir
I. A. Kudryavtsev
A. A. Mitrofanov
A. Kh. Bekyashev
N. E. Arnotskaya
author_sort V. E. Shevchenko
collection DOAJ
description Introduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic targets, which make it possible to more effectively destroy glioma stem cells, becomes topical. In this regard, the study of ferroptosis (FP), which can cause the death of tumor cells with a highly malignant phenotype, is of great importance. However, FP and its regulatory pathways in the GSC are not fully understood. At present, it is also not clear how FP differs for glioma stem cells and glioblastoma differentiated cells.Aim. To study the expression of ferroptosis signaling cascade determinants in CD133+ glioma stem cells and CD133- glioblastoma differentiated cells using high resolution proteomic mass spectrometry.Materials and methods. High-resolution proteomic mass spectrometry, cell technologies.Results. In total, 1970 proteins were identified, 15 of which are associated with ferroptosis and are present in both cell populations. Upregulation of 12 FP determinants (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) was found in CD133+ glioblastoma stem cells compared to CD133- differential glioblastoma cells, 10 of which were more than 2-fold overexpressed.Conclusion. Important regularities have been established in the expression of ferroptosis determinants and proteins controlling this process in glioma stem cells, which can be used in the development of new approaches to the detection of potential targets for the therapy of glioblastoma multiforme.
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issn 2313-805X
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language Russian
publishDate 2022-10-01
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series Успехи молекулярной онкологии
spelling doaj-art-4ed35bbddfe14f3d9a46750dd338e9222025-08-20T03:22:00ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872022-10-0193606810.17650/2313-805X-2022-9-3-60-68252Ferroptosis determinants - potential therapeutic targets glioblastoma stem cellsV. E. Shevchenko0Z. N. Nikiforova1T. I. Kushnir2I. A. Kudryavtsev3A. A. Mitrofanov4A. Kh. Bekyashev5N. E. Arnotskaya6N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaRussian State Center for Animal Feed and Drug Standardization and QualityN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaIntroduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic targets, which make it possible to more effectively destroy glioma stem cells, becomes topical. In this regard, the study of ferroptosis (FP), which can cause the death of tumor cells with a highly malignant phenotype, is of great importance. However, FP and its regulatory pathways in the GSC are not fully understood. At present, it is also not clear how FP differs for glioma stem cells and glioblastoma differentiated cells.Aim. To study the expression of ferroptosis signaling cascade determinants in CD133+ glioma stem cells and CD133- glioblastoma differentiated cells using high resolution proteomic mass spectrometry.Materials and methods. High-resolution proteomic mass spectrometry, cell technologies.Results. In total, 1970 proteins were identified, 15 of which are associated with ferroptosis and are present in both cell populations. Upregulation of 12 FP determinants (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) was found in CD133+ glioblastoma stem cells compared to CD133- differential glioblastoma cells, 10 of which were more than 2-fold overexpressed.Conclusion. Important regularities have been established in the expression of ferroptosis determinants and proteins controlling this process in glioma stem cells, which can be used in the development of new approaches to the detection of potential targets for the therapy of glioblastoma multiforme.https://umo.abvpress.ru/jour/article/view/459glioblastoma stem cellsferroptosisglioblastoma multiformeproteomemass spectrometry
spellingShingle V. E. Shevchenko
Z. N. Nikiforova
T. I. Kushnir
I. A. Kudryavtsev
A. A. Mitrofanov
A. Kh. Bekyashev
N. E. Arnotskaya
Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
Успехи молекулярной онкологии
glioblastoma stem cells
ferroptosis
glioblastoma multiforme
proteome
mass spectrometry
title Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
title_full Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
title_fullStr Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
title_full_unstemmed Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
title_short Ferroptosis determinants - potential therapeutic targets glioblastoma stem cells
title_sort ferroptosis determinants potential therapeutic targets glioblastoma stem cells
topic glioblastoma stem cells
ferroptosis
glioblastoma multiforme
proteome
mass spectrometry
url https://umo.abvpress.ru/jour/article/view/459
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AT znnikiforova ferroptosisdeterminantspotentialtherapeutictargetsglioblastomastemcells
AT tikushnir ferroptosisdeterminantspotentialtherapeutictargetsglioblastomastemcells
AT iakudryavtsev ferroptosisdeterminantspotentialtherapeutictargetsglioblastomastemcells
AT aamitrofanov ferroptosisdeterminantspotentialtherapeutictargetsglioblastomastemcells
AT akhbekyashev ferroptosisdeterminantspotentialtherapeutictargetsglioblastomastemcells
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