Transforming growth factor-β mimics the key proteome properties of CD133− differentiated and CD133+ cancer stem cells in glioblastoma

Bryukhovetskiy, Igor; Шевченко, В. Е.; Arnotskaya, N. E.; Kushnir, Tatyana; Pak, Oleg; Zgoda, Victor G.; Zaitsev, Sergei; Bryukhovetskiy, Andrey; Sharma, Aruna; Sharma, Hari Shanker

doi:10.1016/bs.irn.2020.03.007

Cited by 5 publications

(6 citation statements)

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“…This demonstrated that ECM and immune in ammation reactions played the key role in occurrence, invasion and metastasis of GBM. The TGF-β in the tumor tissues can inhibit immune cells, decrease local in ammation, and promote the reconstruction of ECM [32]. ECM components and high expression levels on the corresponding cell surface receptors are closely related with the progression of GBM [33].…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-related Prognosis Model, Immunocyte Infiltration Characterization, and Competing Endogenous RNA Network of Glioblastoma

Ding

Peng

et al. 2021

Preprint

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Background: Glioblastoma (GBM) has a high incidence rate, invasive growth, and easy recurrence, and the current therapeutic effect is less than satisfying. Pyroptosis plays an important role in morbidity and progress of GBM. Meanwhile, the tumor microenvironment (TME) is involved in the progress and treatment tolerance of GBM. In the present study, we analyzed prognosis model, immunocyte infiltration characterization, and competing endogenous RNA (ceRNA) network of GBM on the basis of pyroptosis-related genes (PRGs).Methods: The transcriptome and clinical data of 155 patients with GBM and 120 normal subjects were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Lasso (Least absolute shrinkage and selection operator) Cox expression analysis was used in predicting prognostic markers, and its predictive ability was tested using a nomogram. A prognostic risk score formula was constructed, and CIBERSORT, ssGSEA algorithm, Tumor IMmune Estimation Resource (TIMER), and TISIDB database were used in evaluating the immunocyte infiltration characterization and tumor immune response of differential risk samples. A ceRNA network was constructed with Starbase, mirtarbase, and lncbase, and the mechanism of this regulatory axis was explored using Gene Set Enrichment Analysis (GSEA). Results: Five PRGs (CASP3, NLRP2, TP63, GZMB, and CASP9) were identified as the independent prognostic biomarkers of GBM. Prognostic risk score formula analysis showed that the low-risk group had obvious survival advantage compared with the high-risk group, and significant differences in immunocyte infiltration and immune related function score were found. In addition, a ceRNA network of messenger RNA (CASP3, TP63)–microRNA (hsa-miR-519c-5p)–long noncoding RNA (GABPB1-AS1) was established. GSEA analysis showed that the regulatory axis played a considerable role in the extracellular matrix (ECM) and immune inflammatory response.Conclusions: Pyroptosis and TME-related independent prognostic markers were screened in this study, and a prognosis risk score formula was established for the first time according to the prognosis PRGs. TME immunocyte infiltration characterization and immune response were assessed using ssGSEA, CIBERSORT algorithm, TIMER, and TISIDB database. Besides a ceRNA network was built up. This study not only laid foundations for further exploring pyroptosis and TME in improving prognosis of GBM, but also provided a new idea for more effective guidance on clinical immunotherapy to patients and developing new immunotherapeutic drugs.

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Section: Discussionmentioning

confidence: 99%

Pyroptosis-related Prognosis Model, Immunocyte Infiltration Characterization, and Competing Endogenous RNA Network of Glioblastoma

Ding

Peng

et al. 2021

Preprint

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“…Optimum targets may also include ECM components secreted by CSCs, such as collagen type VI α1, laminin β1, fibronectin 1 and tenascin. Targeting these elements may inhibit the development of the CSC niche, and disrupt the corresponding intercellular interactions mediated by these cells (105). This method may be possible using the technologies of adaptive and active IT.…”

Section: It and Csc Controlmentioning

confidence: 99%

Cell‑based immunotherapy of glioblastoma multiforme (Review)

Bryukhovetskiy

2022

Oncol Lett

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Glioblastoma multiforme (GBM) is the most aggressive and lethal primary glial brain tumor. It has an unfavorable prognosis and relatively ineffective treatment protocols, with the median survival of patients being ~15 months. Tumor resistance to treatment is associated with its cancer stem cells (CSCs). At present, there is no medication or technologies that have the ability to completely eradicate CSCs, and immunotherapy (IT) is only able to prolong the patient's life. The present review aimed to investigate systemic solutions for issues associated with immunosuppression, such as ineffective IT and the creation of optimal conditions for CSCs to fulfill their lethal potential. The present review also investigated the main methods involved in local immunosuppression treatment, and highlighted the associated disadvantages. In addition, novel treatment options and targets for the elimination and regulation of CSCs with adaptive and active IT are discussed. Antagonists of TGF-β inhibitors, immune checkpoints and other targeted medication are also summarized. The role of normal hematopoietic stem cells (HSCs) in the mechanisms underlying systemic immune suppression development in cases of GBM is analyzed, and the potential reprogramming of HSCs during their interaction with cancer cells is discussed. Moreover, the present review emphasizes the importance of the aforementioned interactions in the development of immune tolerance and the inactivation of the immune system in neoplastic processes. The possibility of solving the problem of systemic immunosuppression during transplantation of donor HSCs is discussed. Contents1. Introduction 2. Summary on GBM 3. Treatment resistance factors 4. Immune privilege of the CNS 5. IT and CSC control 6. Adaptive IT 7. Active IT 8. IT and molecular-based therapy 9. HSCs and IT 10. Conclusion Cell-based immunotherapy of glioblastoma multiforme (Review)

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“…Подготовка образцов для масс-спектрометрии. Секретомы опухолевых клеток подвергали ультрафильтрации для удаления низкомолекулярных соединений описанным методом [6] Каждый идентифицированный белок, удовлетворяющий вышеназванным требованиям, классифицировался в соответствии с его биологической ролью в клетке, молекулярной функцией и функциональным классом. Основная часть ДЭБ участвовала в метаболических (GO:0008152) (28,1 %) и клеточных (GO:0009987) (28,8 %) процессах, а также в процессах организации клеточных компонентов, биогенезе (GO:0071840) (10,7 %) и локализации (GO:0051179) (9,4 %) (рис.…”

Section: материалы и методыunclassified

The effect of hypoxia on the secretome of human glioblastoma multiforme cells

Kushnir¹,

Арноцкая²,

Кудрявцев³

et al. 2021

Usp. mol. onkol

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Background. Glioblastoma multiforme (GBM) develops in the hypoxic microenvironment, which plays an important role in the pathogenesis of the disease and is closely associated with tumor growth, development and poor prognosis. Hypoxia increases the resistance of tumor cells (TC) to radiation therapy and chemotherapy, promotes the appearance of an aggressive TC phenotype, leading to the disease recurrence. The molecular mechanism of hypoxic action on the secretome of GBM cells, which is involved in the formation of the tumor microenvironment, remains unclear. Also, markers of the aggressive hypoxia-associated phenotype of tumor cells have not been established. The purpose of research – to study the molecular mechanisms of the hypoxia-associated effect on the secretome of the U251 GBM cells.Materials and method. High resolution proteomic mass spectrometry, cell technologies.Results. A total of 1432 proteins were identified in the secretomes of two types of GBM cells (control and experiment). After the action of hypoxia, statistically significant changes in the expression of 390 proteins were registered. 11 proteins showed increase in expression over two orders of magnitude. The intracellular signaling pathways which are responsible for the hypoxia-associated effects on the U251 GMB cells have been identified.Conclusions. Hypoxia significantly affected the proteomic composition of the GBM cells secretome. Five overexpressed secretome proteins, S100A6, HEY1, ZIP3, S100A4, ZEB2, have been proposed as potential markers of the hypoxiaassociated phenotype of GBM, for which participation in the pathogenesis of glioblastoma multiforme has been previously showed.

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Transforming growth factor-β mimics the key proteome properties of CD133− differentiated and CD133+ cancer stem cells in glioblastoma

Cited by 5 publications

References 63 publications

Pyroptosis-related Prognosis Model, Immunocyte Infiltration Characterization, and Competing Endogenous RNA Network of Glioblastoma

Pyroptosis-related Prognosis Model, Immunocyte Infiltration Characterization, and Competing Endogenous RNA Network of Glioblastoma

Cell‑based immunotherapy of glioblastoma multiforme (Review)

The effect of hypoxia on the secretome of human glioblastoma multiforme cells

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