Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press45910.17650/2313-805X-2022-9-3-60-68RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИFerroptosis determinants - potential therapeutic targets glioblastoma stem cellsДетерминанты ферроптоза - потенциальные терапевтические мишени стволовых клеток глиобластомыhttps://orcid.org/0000-0002-0401-9900ShevchenkoV. E.ШевченкоВ. Е.
Russian Federation

Valeriy E. Shevchenko.

24 Kashirskoe Shosse, Moscow 115478.

Шевченко Валерий Евгеньевич.

115478 Москва, Каширское шоссе, 24.

vshev2015@yandex.ruhttps://orcid.org/0000-0001-7657-3735NikiforovaZ. N.НикифороваЗ. Н.
Russian Federation

5 Zvenigorodskoe Shosse, Moscow 123022.

123022 Москва, Звенигородское шоссе, 5.

https://orcid.org/0000-0001-9626-6847KushnirT. I.КушнирТ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

https://orcid.org/0000-0001-7588-1066KudryavtsevI. A.КудрявцевИ. A.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

https://orcid.org/0000-0002-4125-7342MitrofanovA. A.МитрофановА. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

https://orcid.org/0000-0002-4160-9598BekyashevA. Kh.БекяшевА. Х.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

https://orcid.org/0000-0002-0154-8604ArnotskayaN. E.АрноцкаяН. Е.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478.

115478 Москва, Каширское шоссе, 24.

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииRussian State Center for Animal Feed and Drug Standardization and QualityФГБУ «Всероссийский государственный центр качества и стандартизации»150920229360680710202207102022Copyright ©; 2022, Shevchenko V.E., Nikiforova Z.N., Kushnir T.I., Kudryavtsev I.A., Mitrofanov A.A., Bekyashev A.K., Arnotskaya N.E.Copyright ©; 2022, Шевченко В.Е., Никифорова З.Н., Кушнир Т.И., Кудрявцев И.A., Митрофанов А.А., Бекяшев А.Х., Арноцкая Н.Е.2022Shevchenko V.E., Nikiforova Z.N., Kushnir T.I., Kudryavtsev I.A., Mitrofanov A.A., Bekyashev A.K., Arnotskaya N.E.Шевченко В.Е., Никифорова З.Н., Кушнир Т.И., Кудрявцев И.A., Митрофанов А.А., Бекяшев А.Х., Арноцкая Н.Е.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/459

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.

Введение. Терапия мультиформной глиобластомы остается малоэффективной из-за быстроразвивающихся рецидивов опухоли, обусловленных высоким туморогенным потенциалом, резистентностью к химиолучевой терапии и повышенной диссеминацией стволовых клеток глиобластомы. Актуальной становится идентификация потенциальных терапевтических мишеней, позволяющих более эффективно уничтожать данные клетки. в связи с этим большое значение приобретает изучение ферроптоза (ФП), способного вызывать гибель опухолевых клеток с высокозлокачественным фенотипом. Однако ФП и его регуляторные пути в стволовых клетках глиобластомы до конца не изучены. в настоящее время также не ясно, чем отличается ФП в стволовых и дифференцированных клетках глиобластомы.

Цель исследования - методом протеомной масс-спектрометрии высокого разрешения изучить экспрессию детерминант сигнального каскада ФП в CD133+-стволовых и CD133--дифференцированных клетках глиобластомы.

Материалы и методы. использовались протеомная масс-спектрометрия высокого разрешения и клеточные технологии.

Результаты. в целом идентифицированы 1970 белков, 15 из которых связаны с ФП и присутствуют в обеих популяциях клеток. Обнаружена положительная регуляция 12 детерминант ФП (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) в CD133+-стволовых клетках глиобластомы по сравнению с CD133- -дифференцированными клетками глиобластомы, 10 из которых имели повышенную более чем в 2 раза экспрессию.

Заключение. Установлены важные закономерности в экспрессии детерминант ФП и протеинов, контролирующих этот процесс в стволовых клетках глиобластомы, которые могут использоваться при разработке новых подходов к обнаружению потенциальных мишеней для терапии мультиформной глиобластомы.

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