MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer

Godlewski, Jakub; Ferrer-Luna, Rubén; Rooj, Arun K.; Mineo, Marco; Ricklefs, Franz; Takeda, Yuji; Nowicki, Michal O.; Salińska, Elżbieta; Nakano, ﻿Ichiro; Lee, Hakho; Weissleder, Ralph; Beroukhim, Rameen; Chiocca, E. Antonio; Bronisz, Agnieszka

doi:10.1016/j.stemcr.2017.04.024

Cited by 63 publications

(54 citation statements)

References 20 publications

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“…In contrast, the mesenchymal subgroup mainly occurred in hypoxic tumor areas, such as pseudopalisading regions or the cellular tumor core. These findings uncovered a spatial dominance of expression subgroups within the GBM environmental landscape (35).…”

Section: Tumor Landscape Is Marked By Regional Differences In Transcrmentioning

confidence: 82%

Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional Heterogeneity in Glioblastoma Multiforme

Heiland

Gaebelein

Börries

et al. 2018

Molecular Cancer Research

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The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes, such as transcriptional and metabolic reprogramming, play an important role in the development of tumor heterogeneity. The current study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment. Creatine treatment and metabolism was further shown to promote a synergistic effect through upregulation of the glycine cleavage system and chemical regulation of prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of reactive oxygen species and change of the α-ketoglutarate/succinate ratio, leading to an inhibition of HIF signaling in primary tumor cell lines. These effects shifted the transcriptional pattern toward a proneural subtype and reduced the rate of cell migration and invasion Transcriptional subclasses of glioblastoma multiforme are heterogeneously distributed within the same tumor. This study uncovered a regulatory function of the tumor microenvironment by metabolism-driven transcriptional reprogramming in infiltrating glioma cells..

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Section: Tumor Landscape Is Marked By Regional Differences In Transcrmentioning

confidence: 82%

Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional Heterogeneity in Glioblastoma Multiforme

Heiland

Gaebelein

Börries

et al. 2018

Molecular Cancer Research

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“…The diversity of transcriptomic profiles observed in glioma cells is mirrored in the EVs derived from these cells. This dynamic EV mediated communication via the transfer of oncogenic proteins, mRNA and miRNA is one of the crucial factors in GBM proliferation and survival (8,9).…”

Section: Glioma Evs Enhance Tumor Proliferation and Survival In Recipmentioning

confidence: 99%

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

et al. 2020

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Glioblastomas (GBM) are highly aggressive primary brain tumors. Complex and dynamic tumor microenvironment (TME) plays a crucial role in the sustained growth, proliferation, and invasion of GBM. Several means of intercellular communication have been documented between glioma cells and the TME, including growth factors, cytokines, chemokines as well as extracellular vesicles (EVs). EVs carry functional genomic and proteomic cargo from their parental cells and deliver that information to surrounding and distant recipient cells to modulate their behavior. EVs are emerging as crucial mediators of establishment and maintenance of the tumor by modulating the TME into a tumor promoting system. Herein we review recent literature in the context of GBM TME and the means by which EVs modulate tumor proliferation, reprogram metabolic activity, induce angiogenesis, escape immune surveillance, acquire drug resistance and undergo invasion. Understanding the multifaceted roles of EVs in the niche of GBM TME will provide invaluable insights into understanding the biology of GBM and provide functional insights into the dynamic EV-mediated intercellular communication during gliomagenesis, creating new opportunities for GBM diagnostics and therapeutics.

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“…It was shown that the intratumoral exchange of miRNA could augment the heterogeneity of patient-derived GSCs. This was reflected in highly heterogeneous profile of miRNA expression in GBM subtypes (88). Moreover, it was reported that the expression of the subtype-enriched miRNAs such as miR-128 within transcriptionally and phenotypically diverse subpopulations of patientderived GSCs is a potent mechanism of bidirectional transitions between GBM subpopulations (89).…”

Section: Networking Between Stem-like Cells' Subpopulations: Heterogementioning

confidence: 99%

Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance

Nawaz

2017

Stem Cell Investig.

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Recent years have witnessed intensive progress in studying extracellular vesicles (EVs), both for understanding their basic biology and contribution to variety of diseases, biomarker discovery, and their potential as gene delivery vectors and source of innovative therapies. As such, stem cell-derived EVs have contributed significant knowledge which led to the development of cell-free therapies in regenerative medicine. Although, the role of stem cell-derived EVs in maintaining stemness, differentiation and repairing tissue injuries is relatively well-understood; however, knowledge about the contribution of stem cell-derived EVs in cancer progression is just emerging. The aim of this review is, therefore, to discuss the recent developments in stem cell-derived EVs and tumor progression, placing a particular focus on non-coding RNA (ncRNA) mediated cancer progression and resistance against therapies. This includes the failure of normal hematopoiesis and the progression of myeloid neoplasms, enhanced capacity of cancer cells to proliferate and metastasize, and the conversion of normal cells into cancer cells, activation of angiogenic pathways and dormancy in cancer cells. These processes are shared by mesenchymal stem cells (MSCs), cancer stem like-cells and cancer cells in an intricate intratumoral network in order to create self-strengthening tumor niche. In this context, EV-ncRNAs serve as mediators to relay bystander effects of secreting cancer stem cells (CSCs) into recipient cells for priming a tumor permissive environment and relaying therapeutic resistance. Collectively, this knowledge will improve our understandings and approaches in finding new therapeutic targets in the context of CSCs, which could be benefited through engineering EVs for innovative therapies.

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MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer

Cited by 63 publications

References 20 publications

Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional Heterogeneity in Glioblastoma Multiforme

Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional Heterogeneity in Glioblastoma Multiforme

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance

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