The Role of SVZ Stem Cells in Glioblastoma

Altmann, Christine; Keller, Stefanie; Schmidt, Mirko H. H.

doi:10.3390/cancers11040448

Cited by 62 publications

(62 citation statements)

References 208 publications

(268 reference statements)

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“…Glioblastoma (GBM) is the most common and aggressive primary CNS tumor (Stupp et al, 2009;Louis et al, 2016;Mendes et al, 2018;Altmann et al, 2019;Ostrom et al, 2019) and it has been included in the group of diffuse astrocytic and oligodendroglial tumors by the 2016 CNS WHO (Louis et al, 2016). It is thought that genetic alterations affecting neuroglial stem or progenitors cells give origin to GBM.…”

Section: Introductionmentioning

confidence: 99%

The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices

Cintio

Baboci

et al. 2020

Front. Neurosci.

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Glioblastoma (GBM) is the most frequent and aggressive primary central nervous system tumor. Surgery followed by radiotherapy and chemotherapy with alkylating agents constitutes standard first-line treatment of GBM. Complete resection of the GBM tumors is generally not possible given its high invasive features. Although this combination therapy can prolong survival, the prognosis is still poor due to several factors including chemoresistance. In recent years, a comprehensive characterization of the GBM-associated molecular signature has been performed. This has allowed the possibility to introduce a more personalized therapeutic approach for GBM, in which novel targeted therapies, including those employing tyrosine kinase inhibitors (TKIs), could be employed. The GBM tumor microenvironment (TME) exerts a key role in GBM tumor progression, in particular by providing an immunosuppressive state with low numbers of tumor-infiltrating lymphocytes (TILs) and other immune effector cell types that contributes to tumor proliferation and growth. The use of immune checkpoint inhibitors (ICIs) has been successfully introduced in numerous advanced cancers as well as promising results have been shown for the use of these antibodies in untreated brain metastases from melanoma and from non-small cell lung carcinoma (NSCLC). Consequently, the use of PD-1/PD-L1 inhibitors has also been proposed in several clinical trials for the treatment of GBM. In the present review, we will outline the main GBM molecular and TME aspects providing also the grounds for novel targeted therapies and immunotherapies using ICIs for GBM.

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Section: Introductionmentioning

confidence: 99%

The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices

Cintio

Baboci

et al. 2020

Front. Neurosci.

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“…Taken together, these studies and others support the idea that NSC-derived EVs may have therapeutic value for the treatment of brain injury or neurodegenerative disease, as reviewed elsewhere [ 81 ], and possibly for the study of longevity. With respect to glioma, brain tumor-propagating cells (BTPCs) are thought to arise from adult NSCs, and the adult NSC niche may support the growth and division of BTPCs [ 82 ]. Thus, understanding how NSCs signal to tumor cells is essential to devise strategies to block tumor cell proliferation.…”

Section: Role Of Evs In the ‘Healthy’ Nervous Systemmentioning

confidence: 99%

The Emerging Role of Extracellular Vesicles in the Glioma Microenvironment: Biogenesis and Clinical Relevance

Balakrishnan

Roy²,

Fleming

et al. 2020

Cancers

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Gliomas are a diverse group of brain tumors comprised of malignant cells (‘tumor’ cells) and non-malignant ‘normal’ cells, including neural (neurons, glia), inflammatory (microglia, macrophage) and vascular cells. Tumor heterogeneity arises in part because, within the glioma mass, both ‘tumor’ and ‘normal’ cells secrete factors that form a unique microenvironment to influence tumor progression. Extracellular vesicles (EVs) are critical mediators of intercellular communication between immediate cellular neighbors and distantly located cells in healthy tissues/organs and in tumors, including gliomas. EVs mediate cell–cell signaling as carriers of nucleic acid, lipid and protein cargo, and their content is unique to cell types and physiological states. EVs secreted by non-malignant neural cells have important physiological roles in the healthy brain, which can be altered or co-opted to promote tumor progression and metastasis, acting in combination with glioma-secreted EVs. The cell-type specificity of EV content means that ‘vesiculome’ data can potentially be used to trace the cell of origin. EVs may also serve as biomarkers to be exploited for disease diagnosis and to assess therapeutic progress. In this review, we discuss how EVs mediate intercellular communication in glioma, and their potential role as biomarkers and readouts of a therapeutic response.

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“…Gliomas are tumors originating from neural stem cells or progenitor cells (Altmann et al 2019). They range from benign and highly-curable pilocytic astrocytomas (World Health Organisation, WHO grade I, GI), through diffuse astrocytomas that could be benign (WHO grade II, GII) or malignant (WHO grade III, GIII) to highly malignant glioblastomas (WHO grade IV, GIV) (Uhlmann et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of differentially expressed genes between various glioma types

Grabowicz

Wilczyński

Kamińska³

et al. 2020

Preprint

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Gliomas are the most frequent primary tumors of the central nervous system (CNS) and encompass two major subgroups: diffuse, malignant gliomas and benign, well differentiated gliomas showing a more circumscribed growth. Genome-wide next generation sequencing studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different types of gliomas improving tumor diagnosis and having important implications for future clinical trials and patient management. We have recently created a unique resource encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we took advantage of a wealth of data from those high-throughput experiments, intersected those data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found a set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing glioma-related genes. Moreover, many genes associated with the cell-matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by the long range contacts with enhancers. Overall, the results presented here demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy. We demonstrated that integration of whole genome epigenetic data with Hi-C data and transcriptomic profiles described in this work, can segregate low and high grade gliomas and reveal new regulatory networks that could explain some of the functional differences between gliomas of different malignancies.HighlightsIntegration of ATAC-seq, ChIP-seq and RNA-seq reveals glioma malignancy-related gene regulatory networks.TADs segmentation contributes to gene-epigenetically modified enhancer relationships.Contacts of active enhancers in gliomas of different malignancies might affect expression of genes involved in cancerogenesis, such as PROTOCADHERINs or EGFR.

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The Role of SVZ Stem Cells in Glioblastoma

Cited by 62 publications

References 208 publications

The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices

The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices

The Emerging Role of Extracellular Vesicles in the Glioma Microenvironment: Biogenesis and Clinical Relevance

Epigenetic regulation of differentially expressed genes between various glioma types

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