Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles

Gao, Xiaofei; Zhang, Zhaohuan; Mashimo, Tomoyuki; Shen, Bo; Nyagilo, James O.; Wang, Hao; Wang, Yihui; Liu, Zhida; Mulgaonkar, Aditi; Hu, Xiao; Piccirillo, Sara Grazia Maria; Eskiocak, Uğur; Davé, Digant P.; Qin, Song; Yang, Yongjie; Sun, Xiankai; Fu, Yang Xin; Zong, Hui; Sun, Wenzhi; Bachoo, Robert; Ge, Woo Ping

doi:10.1016/j.celrep.2020.01.089

Cited by 75 publications

(74 citation statements)

References 72 publications

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“…Extracellular vesicles (EVs) are nano-sized lipid bilayer vesicles (40-1000nm in diameter) released by cells or detached from the plasma membrane [50,51]. EVs are generally divided into two categories: ectosomes and exosomes.…”

Section: The Biosynthesis and Function Of Extracellular Vesicles And mentioning

confidence: 99%

“…During the progression of the tumor, primary tumorderived exosomal miRNAs can be transferred to nonmalignant cells in the tumor microenvironment to induce heterogeneity [50,[87][88][89]. At the same time, with the changes in biological activity of non-malignant cells in the tumor microenvironment, non-malignant cells can also secrete exosomal miRNAs to further regulate tumor cells or other microenvironmental components [40,90].…”

Section: The Role Of Exosomal Mirnas In Tmementioning

confidence: 99%

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Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

138

117

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Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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Section: The Biosynthesis and Function Of Extracellular Vesicles And mentioning

confidence: 99%

Section: The Role Of Exosomal Mirnas In Tmementioning

confidence: 99%

Exosomal miRNAs in tumor microenvironment

Tan

Xia

et al. 2020

J Exp Clin Cancer Res

138

117

View full text Add to dashboard Cite

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“…Rab27a/b knockdown in astrocytes, which reduces EV secretion, blocks the metastasis of breast cancer cells to the brain 58 . Moreover, knockdown of Rab27a/b in an astrocyte-derived glioma cell line blocked glioma growth in vivo in mouse xenografts 59 . A likely cause of these different effects is that EV cargo is well known to differ based on the cell of origin 60 .…”

Section: Discussionmentioning

confidence: 98%

SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

Balakrishnan

Adnani

Chinchalongporn

et al. 2020

Preprint

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Oligodendrogliomas are lower-grade, slow-growing gliomas that are ultimately fatal. Although driver mutations are known, the mechanisms underlying their signature slow growth rates are poorly understood. We found evidence for intra-tumoral interactions between neoplastic and nonneoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived oligodendroglioma cell lines of lower and higher aggressivity. Both oligodendroglioma cell lines released extracellular vesicles that had cytotoxic effects on nonneoplastic and neoplastic cells, but each had distinct vesicular proteomes. Consistent with extracellular vesicles mediating growth inhibitory effects in oligodendrogliomas, higher expression levels of several extracellular vesicle biogenesis genes (SMPD3,TSG101, STAM1) correlates with longer survival in oligodendroglioma patients. Furthermore, SMPD3 overexpression slows oligodendroglioma cell growth in culture. Conversely, SMPD3 knockdown enhances oligodendroglioma proliferation in vitro, in murine xenografts, and in human cerebral organoid co-cultures. Oligodendroglioma-derived extracellular vesicles thus mediate tumor cell microenvironmental interactions that contribute to low aggressivity.

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“…GBM interacts with several cell types, encompassing endothelial cells, perivascular pericytes, astrocytes, and immune cells [31]. This intercellular communication may occur in various ways, either through a direct cell contact (i.e., tunneling nanotubes, gap junctions) or through cell-to-cell transfer of insoluble cargoes via the release of EVs, such as microvesicles (MVs) and exosomes [34,40,96,97]. Although EVs may differ in morphology and biological effects, they represent a unique way of long-distance, contact-independent, mechanism of intercellular communication, acting as mediators in the crosstalk between GBM and the surrounding TME.…”

Section: The Role Of Mtor-dependent Gscs-derived Evsmentioning

confidence: 99%

“…Remarkably, these cells are the main targets for EVs released from GSCs (Figure 2). Furthermore, EVs released by surrounding stromal cells maintain a supportive niche, which enhances GSC proliferation and aggressiveness [97]. Therefore, these cells are not mere bystanders, but they emerge as active players in GBM TME adaptive remodeling by establishing a dynamic EV-mediated crosstalk with GSCs [123].…”

Section: Mtor-dependent Evs Effects On Glioma-associated Parenchymal mentioning

confidence: 99%

mTOR Modulates Intercellular Signals for Enlargement and Infiltration in Glioblastoma Multiforme

Ryskalin

Biagioni

Lenzi

et al. 2020

Cancers

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Recently, exosomal release has been related to the acquisition of a malignant phenotype in glioblastoma cancer stem cells (GSCs). Remarkably, intriguing reports demonstrate that GSC-derived extracellular vesicles (EVs) contribute to glioblastoma multiforme (GBM) tumorigenesis via multiple pathways by regulating tumor growth, infiltration, and immune invasion. In fact, GSCs release tumor-promoting macrovesicles that can disseminate as paracrine factors to induce phenotypic alterations in glioma-associated parenchymal cells. In this way, GBM can actively recruit different stromal cells, which, in turn, may participate in tumor microenvironment (TME) remodeling and, thus, alter tumor progression. Vice versa, parenchymal cells can transfer their protein and genetic contents to GSCs by EVs; thus, promoting GSCs tumorigenicity. Moreover, GBM was shown to hijack EV-mediated cell-to-cell communication for self-maintenance. The present review examines the role of the mammalian Target of Rapamycin (mTOR) pathway in altering EVs/exosome-based cell-to-cell communication, thus modulating GBM infiltration and volume growth. In fact, exosomes have been implicated in GSC niche maintenance trough the modulation of GSCs stem cell-like properties, thus, affecting GBM infiltration and relapse. The present manuscript will focus on how EVs, and mostly exosomes, may act on GSCs and neighbor non tumorigenic stromal cells to modify their expression and translational profile, while making the TME surrounding the GSC niche more favorable for GBM growth and infiltration. Novel insights into the mTOR-dependent mechanisms regulating EV-mediated intercellular communication within GBM TME hold promising directions for future therapeutic applications.

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Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles

Cited by 75 publications

References 72 publications

Exosomal miRNAs in tumor microenvironment

Exosomal miRNAs in tumor microenvironment

SMPD3suppresses IDH mutant tumor growth via dual autocrine-paracrine roles

mTOR Modulates Intercellular Signals for Enlargement and Infiltration in Glioblastoma Multiforme

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